Neurology

  • Article
    | Open Access

    Mutations in the TRPV4 channel cause inherited neurodegeneration syndromes, but the molecular mechanisms are unknown. Here the authors reveal that TRPV4 activation causes dose-dependent, CaMKII-mediated neuronal dysfunction and axonal degeneration via disruption of mitochondrial axonal transport.

    • Brian M. Woolums
    • , Brett A. McCray
    • , Hyun Sung
    • , Masashi Tabuchi
    • , Jeremy M. Sullivan
    • , Kendra Takle Ruppell
    • , Yunpeng Yang
    • , Catherine Mamah
    • , William H. Aisenberg
    • , Pamela C. Saavedra-Rivera
    • , Bryan S. Larin
    • , Alexander R. Lau
    • , Douglas N. Robinson
    • , Yang Xiang
    • , Mark N. Wu
    • , Charlotte J. Sumner
    •  & Thomas E. Lloyd
  • Article
    | Open Access

    Gut microbiome has been linked to cavernous angioma (CA), a common vascular disease, but the role in humans remains unclear. Here, the authors combine 16S rRNA sequencing and shotgun metagenomics to profile the microbiome in a large cohort of human subjects with and without CA, and among subjects with different CA clinical features.

    • Sean P. Polster
    • , Anukriti Sharma
    • , Ceylan Tanes
    • , Alan T. Tang
    • , Patricia Mericko
    • , Ying Cao
    • , Julián Carrión-Penagos
    • , Romuald Girard
    • , Janne Koskimäki
    • , Dongdong Zhang
    • , Agnieszka Stadnik
    • , Sharbel G. Romanos
    • , Seán B. Lyne
    • , Robert Shenkar
    • , Kimberly Yan
    • , Cornelia Lee
    • , Amy Akers
    • , Leslie Morrison
    • , Myranda Robinson
    • , Atif Zafar
    • , Kyle Bittinger
    • , Helen Kim
    • , Jack A. Gilbert
    • , Mark L. Kahn
    • , Le Shen
    •  & Issam A. Awad
  • Article
    | Open Access

    Semantic dementia patients present with a core semantic impairment and variations of language, behavioural and face recognition abilities. Here, the authors build a unified multidimensional model to capture all these graded symptoms and map them to the variations in the patients’ frontotemporal atrophy.

    • Junhua Ding
    • , Keliang Chen
    • , Haoming Liu
    • , Lin Huang
    • , Yan Chen
    • , Yingru Lv
    • , Qing Yang
    • , Qihao Guo
    • , Zaizhu Han
    •  & Matthew. A. Lambon Ralph
  • Article
    | Open Access

    Following ischemic insult, neovascularization and vascular remodelling play an essential part in the repair of brain damage. Here the authors show that neutrophil extracellular traps serve a detrimental role in the regeneration process, limiting the functional recovery of the brain post injury.

    • Lijing Kang
    • , Huilin Yu
    • , Xing Yang
    • , Yuanbo Zhu
    • , Xiaofei Bai
    • , Ranran Wang
    • , Yongliang Cao
    • , Haochen Xu
    • , Haiyu Luo
    • , Lu Lu
    • , Mei-Juan Shi
    • , Yujing Tian
    • , Wenying Fan
    •  & Bing-Qiao Zhao
  • Article
    | Open Access

    Kinesins regulate intracellular transport and microtubule dynamics. Here, the authors show that KIF21B variants in humans associate with corpus callosum agenesis and microcephaly. Using mice and zebrafish, they showed the cellular mechanisms altered by the missense KIF21B variants.

    • Laure Asselin
    • , José Rivera Alvarez
    • , Solveig Heide
    • , Camille S. Bonnet
    • , Peggy Tilly
    • , Hélène Vitet
    • , Chantal Weber
    • , Carlos A. Bacino
    • , Kristin Baranaño
    • , Anna Chassevent
    • , Amy Dameron
    • , Laurence Faivre
    • , Neil A. Hanchard
    • , Sonal Mahida
    • , Kirsty McWalter
    • , Cyril Mignot
    • , Caroline Nava
    • , Agnès Rastetter
    • , Haley Streff
    • , Christel Thauvin-Robinet
    • , Marjan M. Weiss
    • , Gladys Zapata
    • , Petra J. G. Zwijnenburg
    • , Frédéric Saudou
    • , Christel Depienne
    • , Christelle Golzio
    • , Delphine Héron
    •  & Juliette D. Godin
  • Article
    | Open Access

    Calvo-Rodriguez et al. show elevated calcium levels in neuronal mitochondria in a mouse model of cerebral β-amyloidosis after plaque deposition, which precede rare neuron death events in this model. The mechanism involves toxic extracellular Aβ oligomers and the mitochondrial calcium uniporter.

    • Maria Calvo-Rodriguez
    • , Steven S. Hou
    • , Austin C. Snyder
    • , Elizabeth K. Kharitonova
    • , Alyssa N. Russ
    • , Sudeshna Das
    • , Zhanyun Fan
    • , Alona Muzikansky
    • , Monica Garcia-Alloza
    • , Alberto Serrano-Pozo
    • , Eloise Hudry
    •  & Brian J. Bacskai
  • Article
    | Open Access

    Cerebral small vessel disease (CSVD) is a major cause of stroke and associated with structural changes of the brain. Here, Persyn et al. perform genome-wide association studies for magnetic resonance imaging (MRI) markers of CSVD, explore genetic correlations and prioritize candidate genes.

    • Elodie Persyn
    • , Ken B. Hanscombe
    • , Joanna M. M. Howson
    • , Cathryn M. Lewis
    • , Matthew Traylor
    •  & Hugh S. Markus
  • Article
    | Open Access

    Noninvasive electromagnetic measurements are utilized effectively to estimate large scale dynamic brain networks. Sohrabpour et al. propose a novel electrophysiological source imaging approach to estimate the location and size of epileptogenic tissues in patients with epilepsy.

    • Abbas Sohrabpour
    • , Zhengxiang Cai
    • , Shuai Ye
    • , Benjamin Brinkmann
    • , Gregory Worrell
    •  & Bin He
  • Article
    | Open Access

    Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD) reflecting abnormal tau metabolism in the AD brain. Here the authors demonstrate that CSF p-tau217 shows better performance as an AD biomarker than p-tau181.

    • Shorena Janelidze
    • , Erik Stomrud
    • , Ruben Smith
    • , Sebastian Palmqvist
    • , Niklas Mattsson
    • , David C. Airey
    • , Nicholas K. Proctor
    • , Xiyun Chai
    • , Sergey Shcherbinin
    • , John R. Sims
    • , Gallen Triana-Baltzer
    • , Clara Theunis
    • , Randy Slemmon
    • , Marc Mercken
    • , Hartmuth Kolb
    • , Jeffrey L. Dage
    •  & Oskar Hansson
  • Article
    | Open Access

    Parkinson’s disease (PD) is a common neurodegenerative disorder with a complex etiology involving genetics and the environment. Here, Vallerga et al. identify two CpG probes associated with PD in a blood cell type-corrected epigenome-wide meta-analysis, implicating the SLC7A11 gene as a plausible biological target.

    • Costanza L. Vallerga
    • , Futao Zhang
    • , Javed Fowdar
    • , Allan F. McRae
    • , Ting Qi
    • , Marta F. Nabais
    • , Qian Zhang
    • , Irfahan Kassam
    • , Anjali K. Henders
    • , Leanne Wallace
    • , Grant Montgomery
    • , Yu-Hsuan Chuang
    • , Steve Horvath
    • , Beate Ritz
    • , Glenda Halliday
    • , Ian Hickie
    • , John B. Kwok
    • , John Pearson
    • , Toni Pitcher
    • , Martin Kennedy
    • , Steven R. Bentley
    • , Peter A. Silburn
    • , Jian Yang
    • , Naomi R. Wray
    • , Simon J. G. Lewis
    • , Tim Anderson
    • , John Dalrymple-Alford
    • , George D. Mellick
    • , Peter M. Visscher
    •  & Jacob Gratten
  • Article
    | Open Access

    The neural circuits through which the substantia nigra pars reticulata (SNr) exerts its role in epilepsy control are not known. Here the authors reveal that a long-range SNr-parafascicular nucleus disinhibitory circuit participates in regulating seizures in temporal lobe epilepsy and inhibition of this circuit can alleviate severity of epileptic seizures.

    • Bin Chen
    • , Cenglin Xu
    • , Yi Wang
    • , Wenkai Lin
    • , Ying Wang
    • , Liying Chen
    • , Heming Cheng
    • , Lingyu Xu
    • , Tingting Hu
    • , Junli Zhao
    • , Ping Dong
    • , Yi Guo
    • , Shihong Zhang
    • , Shuang Wang
    • , Yudong Zhou
    • , Weiwei Hu
    • , Shuming Duan
    •  & Zhong Chen
  • Article
    | Open Access

    Snoring is common in the population and tends to be more prevalent in older and/or male individuals. Here, the authors perform GWAS for habitual snoring, identify 41 genomic loci and explore potential causal relationships with anthropometric and cardiometabolic disease traits.

    • Adrián I. Campos
    • , Luis M. García-Marín
    • , Enda M. Byrne
    • , Nicholas G. Martin
    • , Gabriel Cuéllar-Partida
    •  & Miguel E. Rentería
  • Article
    | Open Access

    Neurofilament (NfL) levels in CSF and blood have been established as a biomarker of neuronal damage in neurodegenerative diseases, and there is an age-dependent increase in NfL levels in CSF. Here the authors demonstrate that serum NfL levels increase in healthy aging people and predict and correlate with brain volume loss.

    • Michael Khalil
    • , Lukas Pirpamer
    • , Edith Hofer
    • , Margarete M. Voortman
    • , Christian Barro
    • , David Leppert
    • , Pascal Benkert
    • , Stefan Ropele
    • , Christian Enzinger
    • , Franz Fazekas
    • , Reinhold Schmidt
    •  & Jens Kuhle
  • Article
    | Open Access

    In this longitudinal study, the authors tracked the course of brain development from birth to adolescence (age 13 years) and examined the effects of very preterm birth. Very preterm children showed slower brain growth from age 0 (term equivalent) to age 7.

    • Deanne K. Thompson
    • , Lillian G. Matthews
    • , Bonnie Alexander
    • , Katherine J. Lee
    • , Claire E. Kelly
    • , Chris L. Adamson
    • , Rod W. Hunt
    • , Jeanie L. Y. Cheong
    • , Megan Spencer-Smith
    • , Jeffrey J. Neil
    • , Marc L. Seal
    • , Terrie E. Inder
    • , Lex W. Doyle
    •  & Peter J. Anderson
  • Article
    | Open Access

    Measures of neural processing can be obtained non-invasively from all areas of the human brain but one, the olfactory bulb. Here, the authors show that signals obtained from EEG electrodes at the nasal bridge represent responses from the human olfactory bulb, the so-called Electrobulbogram.

    • Behzad Iravani
    • , Artin Arshamian
    • , Kathrin Ohla
    • , Donald A. Wilson
    •  & Johan N. Lundström
  • Article
    | Open Access

    Diagnosis of vascular dementia is hampered by the lack of biochemical markers for this disease. Here, the authors show that vascular dementia is associated with increased lipocalin-2 in cerebrospinal fluid, compared to controls and patients with other forms of dementia.

    • Franc Llorens
    • , Peter Hermann
    • , Anna Villar-Piqué
    • , Daniela Diaz-Lucena
    • , Katarina Nägga
    • , Oskar Hansson
    • , Isabel Santana
    • , Matthias Schmitz
    • , Christian Schmidt
    • , Daniela Varges
    • , Stefan Goebel
    • , Julien Dumurgier
    • , Henrik Zetterberg
    • , Kaj Blennow
    • , Claire Paquet
    • , Inês Baldeiras
    • , Isidro Ferrer
    •  & Inga Zerr
  • Article
    | Open Access

    Mechanisms behind molecular transport from cerebrospinal fluid to dural lymphatic vessels remain unknown. This study demonstrates that trans-arachnoid molecular passage does occur and suggests that parasagittal dura may serve as a bridging link between human brain and dural lymphatic vessels.

    • Geir Ringstad
    •  & Per Kristian Eide
  • Article
    | Open Access

    Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

    • Nicolai Franzmeier
    • , Julia Neitzel
    • , Anna Rubinski
    • , Ruben Smith
    • , Olof Strandberg
    • , Rik Ossenkoppele
    • , Oskar Hansson
    • , Michael Ewers
    • , Michael Weiner
    • , Paul Aisen
    • , Ronald Petersen
    • , Clifford R. Jack Jr.
    • , William Jagust
    • , John Q. Trojanowki
    • , Arthur W. Toga
    • , Laurel Beckett
    • , Robert C. Green
    • , Andrew J. Saykin
    • , John Morris
    • , Leslie M. Shaw
    • , Enchi Liu
    • , Tom Montine
    • , Ronald G. Thomas
    • , Michael Donohue
    • , Sarah Walter
    • , Devon Gessert
    • , Tamie Sather
    • , Gus Jiminez
    • , Danielle Harvey
    • , Michael Donohue
    • , Matthew Bernstein
    • , Nick Fox
    • , Paul Thompson
    • , Norbert Schuff
    • , Charles DeCArli
    • , Bret Borowski
    • , Jeff Gunter
    • , Matt Senjem
    • , Prashanthi Vemuri
    • , David Jones
    • , Kejal Kantarci
    • , Chad Ward
    • , Robert A. Koeppe
    • , Norm Foster
    • , Eric M. Reiman
    • , Kewei Chen
    • , Chet Mathis
    • , Susan Landau
    • , Nigel J. Cairns
    • , Erin Householder
    • , Lisa Taylor Reinwald
    • , Virginia Lee
    • , Magdalena Korecka
    • , Michal Figurski
    • , Karen Crawford
    • , Scott Neu
    • , Tatiana M. Foroud
    • , Steven Potkin
    • , Li Shen
    • , Faber Kelley
    • , Sungeun Kim
    • , Kwangsik Nho
    • , Zaven Kachaturian
    • , Richard Frank
    • , Peter J. Snyder
    • , Susan Molchan
    • , Jeffrey Kaye
    • , Joseph Quinn
    • , Betty Lind
    • , Raina Carter
    • , Sara Dolen
    • , Lon S. Schneider
    • , Sonia Pawluczyk
    • , Mauricio Beccera
    • , Liberty Teodoro
    • , Bryan M. Spann
    • , James Brewer
    • , Helen Vanderswag
    • , Adam Fleisher
    • , Judith L. Heidebrink
    • , Joanne L. Lord
    • , Ronald Petersen
    • , Sara S. Mason
    • , Colleen S. Albers
    • , David Knopman
    • , Kris Johnson
    • , Rachelle S. Doody
    • , Javier Villanueva Meyer
    • , Munir Chowdhury
    • , Susan Rountree
    • , Mimi Dang
    • , Yaakov Stern
    • , Lawrence S. Honig
    • , Karen L. Bell
    • , Beau Ances
    • , John C. Morris
    • , Maria Carroll
    • , Sue Leon
    • , Erin Householder
    • , Mark A. Mintun
    • , Stacy Schneider
    • , Angela OliverNG
    • , Randall Griffith
    • , David Clark
    • , David Geldmacher
    • , John Brockington
    • , Erik Roberson
    • , Hillel Grossman
    • , Effie Mitsis
    • , Leyla deToledo-Morrell
    • , Raj C. Shah
    • , Ranjan Duara
    • , Daniel Varon
    • , Maria T. Greig
    • , Peggy Roberts
    • , Marilyn Albert
    • , Chiadi Onyike
    • , Daniel D’Agostino II
    • , Stephanie Kielb
    • , James E. Galvin
    • , Dana M. Pogorelec
    • , Brittany Cerbone
    • , Christina A. Michel
    • , Henry Rusinek
    • , Mony J de Leon
    • , Lidia Glodzik
    • , Susan De Santi
    • , P. Murali Doraiswamy
    • , Jeffrey R. Petrella
    • , Terence Z. Wong
    • , Steven E. Arnold
    • , Jason H. Karlawish
    • , David Wolk
    • , Charles D. Smith
    • , Greg Jicha
    • , Peter Hardy
    • , Partha Sinha
    • , Elizabeth Oates
    • , Gary Conrad
    • , Oscar L. Lopez
    • , MaryAnn Oakley
    • , Donna M. Simpson
    • , Anton P. Porsteinsson
    • , Bonnie S. Goldstein
    • , Kim Martin
    • , Kelly M. Makino
    • , M. Saleem Ismail
    • , Connie Brand
    • , Ruth A. Mulnard
    • , Gaby Thai
    • , Catherine Mc Adams Ortiz
    • , Kyle Womack
    • , Dana Mathews
    • , Mary Quiceno
    • , Ramon Diaz Arrastia
    • , Richard King
    • , Myron Weiner
    • , Kristen Martin Cook
    • , Michael DeVous
    • , Allan I. Levey
    • , James J. Lah
    • , Janet S. Cellar
    • , Jeffrey M. Burns
    • , Heather S. Anderson
    • , Russell H. Swerdlow
    • , Liana Apostolova
    • , Kathleen Tingus
    • , Ellen Woo
    • , Daniel H. S. Silverman
    • , Po H. Lu
    • , George Bartzokis
    • , Neill R Graff Radford
    • , Francine ParfittH
    • , Tracy Kendall
    • , Heather Johnson
    • , Martin R. Farlow
    • , Ann Marie Hake
    • , Brandy R. Matthews
    • , Scott Herring
    • , Cynthia Hunt
    • , Christopher H. van Dyck
    • , Richard E. Carson
    • , Martha G. MacAvoy
    • , Howard Chertkow
    • , Howard Bergman
    • , Chris Hosein
    • , Sandra Black
    • , Bojana Stefanovic
    • , Curtis Caldwell
    • , Ging Yuek Robin Hsiung
    • , Howard Feldman
    • , Benita Mudge
    • , Michele Assaly Past
    • , Andrew Kertesz
    • , John Rogers
    • , Dick Trost
    • , Charles Bernick
    • , Donna Munic
    • , Diana Kerwin
    • , Marek Marsel Mesulam
    • , Kristine Lipowski
    • , Chuang Kuo Wu
    • , Nancy Johnson
    • , Carl Sadowsky
    • , Walter Martinez
    • , Teresa Villena
    • , Raymond Scott Turner
    • , Kathleen Johnson
    • , Brigid Reynolds
    • , Reisa A. Sperling
    • , Keith A. Johnson
    • , Gad Marshall
    • , Meghan Frey
    • , Jerome Yesavage
    • , Joy L. Taylor
    • , Barton Lane
    • , Allyson Rosen
    • , Jared Tinklenberg
    • , Marwan N. Sabbagh
    • , Christine M. Belden
    • , Sandra A. Jacobson
    • , Sherye A. Sirrel
    • , Neil Kowall
    • , Ronald Killiany
    • , Andrew E. Budson
    • , Alexander Norbash
    • , Patricia Lynn Johnson
    • , Thomas O. Obisesan
    • , Saba Wolday
    • , Joanne Allard
    • , Alan Lerner
    • , Paula Ogrocki
    • , Leon Hudson
    • , Evan Fletcher
    • , Owen Carmichael
    • , John Olichney
    • , Charles DeCarli
    • , Smita Kittur
    • , Michael Borrie
    • , T Y Lee
    • , Rob Bartha
    • , Sterling Johnson
    • , Sanjay Asthana
    • , Cynthia M. Carlsson
    • , Steven G. Potkin
    • , Adrian Preda
    • , Dana Nguyen
    • , Pierre Tariot
    • , Adam Fleisher
    • , Stephanie Reeder
    • , Vernice Bates
    • , Horacio Capote
    • , Michelle Rainka
    • , Douglas W. Scharre
    • , Maria Kataki
    • , Anahita Adeli
    • , Earl A. Zimmerman
    • , Dzintra Celmins
    • , Alice D. Brown
    • , Godfrey D. Pearlson
    • , Karen Blank
    • , Karen Anderson
    • , Robert B. Santulli
    • , Tamar J. Kitzmiller
    • , Eben S. Schwartz
    • , Kaycee M. SinkS
    • , Jeff D. Williamson
    • , Pradeep Garg
    • , Franklin Watkins
    • , Brian R. Ott
    • , Henry Querfurth
    • , Geoffrey Tremont
    • , Stephen Salloway
    • , Paul Malloy
    • , Stephen Correia
    • , Howard J. Rosen
    • , Bruce L. Miller
    • , Jacobo Mintzer
    • , Kenneth Spicer
    • , David Bachman
    • , Elizabether Finger
    • , Stephen Pasternak
    • , Irina Rachinsky
    • , John Rogers
    • , Andrew Kertesz
    • , Dick Drost
    • , Nunzio Pomara
    • , Raymundo Hernando
    • , Antero Sarrael
    • , Susan K. Schultz
    • , Laura L. Boles Ponto
    • , Hyungsub Shim
    • , Karen Elizabeth Smith
    • , Norman Relkin
    • , Gloria Chaing
    • , Lisa Raudin
    • , Amanda Smith
    • , Kristin Fargher
    •  & Balebail Ashok Raj
  • Article
    | Open Access

    Stroke risk is influenced by genetic and lifestyle factors and previously a genomic risk score (GRS) for stroke was proposed, albeit with limited predictive power. Here, Abraham et al. develop a metaGRS that is composed of several stroke-related GRSs and demonstrate improved predictive power compared with individual GRS or classic risk factors.

    • Gad Abraham
    • , Rainer Malik
    • , Ekaterina Yonova-Doing
    • , Agus Salim
    • , Tingting Wang
    • , John Danesh
    • , Adam S. Butterworth
    • , Joanna M. M. Howson
    • , Michael Inouye
    •  & Martin Dichgans
  • Article
    | Open Access

    The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has shown efficacy for the treatment of neurofibromatosis type 2 (NF2). Here, the authors show that VEGFRs peptide vaccination can improve hearing and reduce tumor volume in NF2 patients, including in previously bevacizumab resistant tumors.

    • Ryota Tamura
    • , Masato Fujioka
    • , Yukina Morimoto
    • , Kentaro Ohara
    • , Kenzo Kosugi
    • , Yumiko Oishi
    • , Mizuto Sato
    • , Ryo Ueda
    • , Hirokazu Fujiwara
    • , Tetsuro Hikichi
    • , Shinobu Noji
    • , Naoki Oishi
    • , Kaoru Ogawa
    • , Yutaka Kawakami
    • , Takayuki Ohira
    • , Kazunari Yoshida
    •  & Masahiro Toda
  • Article
    | Open Access

    Mutations in Ftkn cause Fukuyama muscular dystrophy, and heart failure is the main cause of death in thes patients. Here the authors show that acute elimination of Fktn in adult mice causes early mortality, and this is associated with myocyte dysfunction, with disorganised Golg-microtubule networks, and that the pathology can be ameliorated with colchicine treatment.

    • Yoshihiro Ujihara
    • , Motoi Kanagawa
    • , Satoshi Mohri
    • , Satomi Takatsu
    • , Kazuhiro Kobayashi
    • , Tatsushi Toda
    • , Keiji Naruse
    •  & Yuki Katanosaka
  • Article
    | Open Access

    Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are characterized by the pathological accumulation of α-synuclein. Here the authors employ fluorescent probes, electron microscopy and NMR spectroscopy to study the properties of α-synuclein aggregates that were amplified from patient brain extracts and observe a greater structural diversity among PD patients compared to MSA patients.

    • Timo Strohäker
    • , Byung Chul Jung
    • , Shu-Hao Liou
    • , Claudio O. Fernandez
    • , Dietmar Riedel
    • , Stefan Becker
    • , Glenda M. Halliday
    • , Marina Bennati
    • , Woojin S. Kim
    • , Seung-Jae Lee
    •  & Markus Zweckstetter
  • Article
    | Open Access

    Many approaches exist to process data from individual imaging modalities, but integrating them is challenging. The authors develop an automated resource that enables co-registered network- and tract-level analysis of macroscopic in-vivo imaging and microscopic imaging of cleared tissue.

    • Maged Goubran
    • , Christoph Leuze
    • , Brian Hsueh
    • , Markus Aswendt
    • , Li Ye
    • , Qiyuan Tian
    • , Michelle Y. Cheng
    • , Ailey Crow
    • , Gary K. Steinberg
    • , Jennifer A. McNab
    • , Karl Deisseroth
    •  & Michael Zeineh
  • Article
    | Open Access

    Parkinson’s disease (PD) is characterized by neurodegeneration associated with loss of dopaminergic (DA) neurons and deposition of Lewy bodies. Here, Wang et al. use co-expression network analysis to pinpoint disease pathways and propose reduced expression of STMN2 as a cause of presynaptic function loss in PD.

    • Qian Wang
    • , Yuanxi Zhang
    • , Minghui Wang
    • , Won-Min Song
    • , Qi Shen
    • , Andrew McKenzie
    • , Insup Choi
    • , Xianxiao Zhou
    • , Ping-Yue Pan
    • , Zhenyu Yue
    •  & Bin Zhang
  • Article
    | Open Access

    T cells from narcolepsy patients were recently reported to recognize hypocretin, a wakefulness-promoting neurohormone, suggesting autoimmune origin of the disease. Here the authors show that hypocretin-specific T cells expand both in healthy controls and in narcolepsy patients, and identify preliminary features that may distinguish them.

    • Wei Jiang
    • , James R. Birtley
    • , Shu-Chen Hung
    • , Weiqi Wang
    • , Shin-Heng Chiou
    • , Claudia Macaubas
    • , Birgitte Kornum
    • , Lu Tian
    • , Huang Huang
    • , Lital Adler
    • , Grant Weaver
    • , Liying Lu
    • , Alexandra Ilstad-Minnihan
    • , Sriram Somasundaram
    • , Sashi Ayyangar
    • , Mark M. Davis
    • , Lawrence J. Stern
    •  & Elizabeth D. Mellins
  • Article
    | Open Access

    The risk of fatal stroke is increased in children, adolescent, and young (<40 years) cancer patients after diagnosis. Here, the authors report a retrospective, population-based study and show that the risk of stroke among cancer patients is twice that of the general population and rises with longer follow up time.

    • Nicholas G. Zaorsky
    • , Ying Zhang
    • , Leila T. Tchelebi
    • , Heath B. Mackley
    • , Vernon M. Chinchilli
    •  & Brad E. Zacharia
  • Article
    | Open Access

    Familial cortical myoclonic tremor (FAME) has so far been mapped to regions on chromosome 2, 3, 5 and 8 and pentameric repeat expansions in SAMD12 were identified as cause of FAME1. Here, Corbett et al. identify ATTTT/ATTTC repeat expansions in intron 1 of STARD7 in individuals with FAME2.”

    • Mark A. Corbett
    • , Thessa Kroes
    • , Liana Veneziano
    • , Mark F. Bennett
    • , Rahel Florian
    • , Amy L. Schneider
    • , Antonietta Coppola
    • , Laura Licchetta
    • , Silvana Franceschetti
    • , Antonio Suppa
    • , Aaron Wenger
    • , Davide Mei
    • , Manuela Pendziwiat
    • , Sabine Kaya
    • , Massimo Delledonne
    • , Rachel Straussberg
    • , Luciano Xumerle
    • , Brigid Regan
    • , Douglas Crompton
    • , Anne-Fleur van Rootselaar
    • , Anthony Correll
    • , Rachael Catford
    • , Francesca Bisulli
    • , Shreyasee Chakraborty
    • , Sara Baldassari
    • , Paolo Tinuper
    • , Kirston Barton
    • , Shaun Carswell
    • , Martin Smith
    • , Alfredo Berardelli
    • , Renee Carroll
    • , Alison Gardner
    • , Kathryn L. Friend
    • , Ilan Blatt
    • , Michele Iacomino
    • , Carlo Di Bonaventura
    • , Salvatore Striano
    • , Julien Buratti
    • , Boris Keren
    • , Caroline Nava
    • , Sylvie Forlani
    • , Gabrielle Rudolf
    • , Edouard Hirsch
    • , Eric Leguern
    • , Pierre Labauge
    • , Simona Balestrini
    • , Josemir W. Sander
    • , Zaid Afawi
    • , Ingo Helbig
    • , Hiroyuki Ishiura
    • , Shoji Tsuji
    • , Sanjay M. Sisodiya
    • , Giorgio Casari
    • , Lynette G. Sadleir
    • , Riaan van Coller
    • , Marina A. J. Tijssen
    • , Karl Martin Klein
    • , Arn M. J. M. van den Maagdenberg
    • , Federico Zara
    • , Renzo Guerrini
    • , Samuel F. Berkovic
    • , Tommaso Pippucci
    • , Laura Canafoglia
    • , Melanie Bahlo
    • , Pasquale Striano
    • , Ingrid E. Scheffer
    • , Francesco Brancati
    • , Christel Depienne
    •  & Jozef Gecz
  • Article
    | Open Access

    Familial cortical myoclonic tremor with epilepsy (FAME) is a slowly progressing cortical tremor mapping to various genomic loci, including intronic expansions in SAMD12 for FAME1. Here, Florian et al. describe mixed intronic TTTTA/TTTCA expansions of various lengths in the first intron of MARCH6 as a cause of FAME3.

    • Rahel T. Florian
    • , Florian Kraft
    • , Elsa Leitão
    • , Sabine Kaya
    • , Stephan Klebe
    • , Eloi Magnin
    • , Anne-Fleur van Rootselaar
    • , Julien Buratti
    • , Theresa Kühnel
    • , Christopher Schröder
    • , Sebastian Giesselmann
    • , Nikolai Tschernoster
    • , Janine Altmueller
    • , Anaide Lamiral
    • , Boris Keren
    • , Caroline Nava
    • , Delphine Bouteiller
    • , Sylvie Forlani
    • , Ludmila Jornea
    • , Regina Kubica
    • , Tao Ye
    • , Damien Plassard
    • , Bernard Jost
    • , Vincent Meyer
    • , Jean-François Deleuze
    • , Yannick Delpu
    • , Mario D. M. Avarello
    • , Lisanne S. Vijfhuizen
    • , Gabrielle Rudolf
    • , Edouard Hirsch
    • , Thessa Kroes
    • , Philipp S. Reif
    • , Felix Rosenow
    • , Christos Ganos
    • , Marie Vidailhet
    • , Lionel Thivard
    • , Alexandre Mathieu
    • , Thomas Bourgeron
    • , Ingo Kurth
    • , Haloom Rafehi
    • , Laura Steenpass
    • , Bernhard Horsthemke
    • , Samuel F. Berkovic
    • , Francesca Bisulli
    • , Francesco Brancati
    • , Laura Canafoglia
    • , Giorgio Casari
    • , Renzo Guerrini
    • , Hiroyuki Ishiura
    • , Laura Licchetta
    • , Davide Mei
    • , Tommaso Pippucci
    • , Lynette Sadleir
    • , Ingrid E. Scheffer
    • , Pasquale Striano
    • , Paolo Tinuper
    • , Shoji Tsuji
    • , Federico Zara
    • , Eric LeGuern
    • , Karl Martin Klein
    • , Pierre Labauge
    • , Mark F. Bennett
    • , Melanie Bahlo
    • , Jozef Gecz
    • , Mark A. Corbett
    • , Marina A. J. Tijssen
    • , Arn M. J. M. van den Maagdenberg
    •  & Christel Depienne
  • Article
    | Open Access

    Deposition of tau protein aggregates occurs during aging and Alzheimer disease. Here, the authors show that tau burden in the anterior-temporal memory network is associated with disrupted fMRI connectivity and functional isolation of the hippocampus from other memory network components.

    • Theresa M. Harrison
    • , Anne Maass
    • , Jenna N. Adams
    • , Richard Du
    • , Suzanne L. Baker
    •  & William J. Jagust
  • Article
    | Open Access

    Disturbances in IP3 receptor-mediated release of Ca2+ from the endoplasmatic reticulum are associated with neurodegenerative disease. Here, the authors identify in four families with hereditary spastic paraplegia biallelic mutations in RNF170 that associate with increased basal levels of IP3 receptors.

    • Matias Wagner
    • , Daniel P. S. Osborn
    • , Ina Gehweiler
    • , Maike Nagel
    • , Ulrike Ulmer
    • , Somayeh Bakhtiari
    • , Rim Amouri
    • , Reza Boostani
    • , Faycal Hentati
    • , Maryam M. Hockley
    • , Benedikt Hölbling
    • , Thomas Schwarzmayr
    • , Ehsan Ghayoor Karimiani
    • , Christoph Kernstock
    • , Reza Maroofian
    • , Wolfgang Müller-Felber
    • , Ege Ozkan
    • , Sergio Padilla-Lopez
    • , Selina Reich
    • , Jennifer Reichbauer
    • , Hossein Darvish
    • , Neda Shahmohammadibeni
    • , Abbas Tafakhori
    • , Katharina Vill
    • , Stephan Zuchner
    • , Michael C. Kruer
    • , Juliane Winkelmann
    • , Yalda Jamshidi
    •  & Rebecca Schüle
  • Article
    | Open Access

    Neurodevelopmental disorders (NDDs) are a heterogeneous group of diseases for which the genetic basis is still unknown in more than half of the cases. Here, the authors report a NDD associated with disruptive variants in the TANC2 gene and show that rols, the TANC2 homolog in flies, is required for synapse growth and function.

    • Hui Guo
    • , Elisa Bettella
    • , Paul C. Marcogliese
    • , Rongjuan Zhao
    • , Jonathan C. Andrews
    • , Tomasz J. Nowakowski
    • , Madelyn A. Gillentine
    • , Kendra Hoekzema
    • , Tianyun Wang
    • , Huidan Wu
    • , Sharayu Jangam
    • , Cenying Liu
    • , Hailun Ni
    • , Marjolein H. Willemsen
    • , Bregje W. van Bon
    • , Tuula Rinne
    • , Servi J. C. Stevens
    • , Tjitske Kleefstra
    • , Han G. Brunner
    • , Helger G. Yntema
    • , Min Long
    • , Wenjing Zhao
    • , Zhengmao Hu
    • , Cindy Colson
    • , Nicolas Richard
    • , Charles E. Schwartz
    • , Corrado Romano
    • , Lucia Castiglia
    • , Maria Bottitta
    • , Shweta U. Dhar
    • , Deanna J. Erwin
    • , Lisa Emrick
    • , Boris Keren
    • , Alexandra Afenjar
    • , Baosheng Zhu
    • , Bing Bai
    • , Pawel Stankiewicz
    • , Kristin Herman
    • , Deborah A. Nickerson
    • , Michael J. Bamshad
    • , Saadet Mercimek-Andrews
    • , Jane Juusola
    • , Amy B. Wilfert
    • , Rami Abou Jamra
    • , Benjamin Büttner
    • , Heather C. Mefford
    • , Alison M. Muir
    • , Ingrid E. Scheffer
    • , Brigid M. Regan
    • , Stephen Malone
    • , Jozef Gecz
    • , Jan Cobben
    • , Marjan M. Weiss
    • , Quinten Waisfisz
    • , Emilia K. Bijlsma
    • , Mariëtte J. V. Hoffer
    • , Claudia A. L. Ruivenkamp
    • , Stefano Sartori
    • , Fan Xia
    • , Jill A. Rosenfeld
    • , Raphael A. Bernier
    • , Michael F. Wangler
    • , Shinya Yamamoto
    • , Kun Xia
    • , Alexander P. A. Stegmann
    • , Hugo J. Bellen
    • , Alessandra Murgia
    •  & Evan E. Eichler
  • Article
    | Open Access

    Retrotransposition events have been linked to some human disorders. Here, Gardner et al. systematically search for mobile genetic elements (ME) in trio whole exome-sequencing datasets and ascertain 9 de novo MEs and further estimate genome-wide germline ME burden and constraint.

    • Eugene J. Gardner
    • , Elena Prigmore
    • , Giuseppe Gallone
    • , Petr Danecek
    • , Kaitlin E. Samocha
    • , Juliet Handsaker
    • , Sebastian S. Gerety
    • , Holly Ironfield
    • , Patrick J. Short
    • , Alejandro Sifrim
    • , Tarjinder Singh
    • , Kate E. Chandler
    • , Emma Clement
    • , Katherine L. Lachlan
    • , Katrina Prescott
    • , Elisabeth Rosser
    • , David R. FitzPatrick
    • , Helen V. Firth
    •  & Matthew E. Hurles
  • Article
    | Open Access

    How do diversity (entropy) and integration of activity across brain regions interact to support consciousness? Here the authors show that anaesthetised individuals and patients with disorders of consciousness exhibit overlapping reductions in both diversity and integration in the brain’s default mode network.

    • Andrea I. Luppi
    • , Michael M. Craig
    • , Ioannis Pappas
    • , Paola Finoia
    • , Guy B. Williams
    • , Judith Allanson
    • , John D. Pickard
    • , Adrian M. Owen
    • , Lorina Naci
    • , David K. Menon
    •  & Emmanuel A. Stamatakis
  • Article
    | Open Access

    Spinal and bulbar muscular atrophy is a neuromuscular disease caused by an expanded CAG repeat in the androgen receptor gene. Here the authors show that Src kinase signaling is activated in a mouse model of the disease, and that Src inhibition improves pathology and behavioral symptoms in mice.

    • Madoka Iida
    • , Kentaro Sahashi
    • , Naohide Kondo
    • , Hideaki Nakatsuji
    • , Genki Tohnai
    • , Yutaka Tsutsumi
    • , Seiya Noda
    • , Ayuka Murakami
    • , Kazunari Onodera
    • , Yohei Okada
    • , Masahiro Nakatochi
    • , Yuka Tsukagoshi Okabe
    • , Shinobu Shimizu
    • , Masaaki Mizuno
    • , Hiroaki Adachi
    • , Hideyuki Okano
    • , Gen Sobue
    •  & Masahisa Katsuno
  • Article
    | Open Access

    While energy metabolism has been repeatedly linked to ALS, motor neuron metabolism remains poorly studied. Here, authors show that human iPSCs rewire specific metabolic routes when they differentiate into functional motor neurons and that ALS-causing mutations in FUS do not affect energy metabolism.

    • Tijs Vandoorne
    • , Koen Veys
    • , Wenting Guo
    • , Adria Sicart
    • , Katlijn Vints
    • , Ann Swijsen
    • , Matthieu Moisse
    • , Guy Eelen
    • , Natalia V. Gounko
    • , Laura Fumagalli
    • , Raheem Fazal
    • , Christine Germeys
    • , Annelies Quaegebeur
    • , Sarah-Maria Fendt
    • , Peter Carmeliet
    • , Catherine Verfaillie
    • , Philip Van Damme
    • , Bart Ghesquière
    • , Katrien De Bock
    •  & Ludo Van Den Bosch
  • Article
    | Open Access

    Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here, authors show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity and can be targeted to rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansion

    • Anthony Giampetruzzi
    • , Eric W. Danielson
    • , Valentina Gumina
    • , Maryangel Jeon
    • , Sivakumar Boopathy
    • , Robert H. Brown
    • , Antonia Ratti
    • , John E. Landers
    •  & Claudia Fallini
  • Article
    | Open Access

    A main symptom of chronic insufficient sleep is excessive daytime sleepiness. Here, Wang et al. report 42 genome-wide significant loci for self-reported daytime sleepiness in 452,071 individuals from the UK Biobank that cluster into two biological subtypes of either sleep propensity or sleep fragmentation.

    • Heming Wang
    • , Jacqueline M. Lane
    • , Samuel E. Jones
    • , Hassan S. Dashti
    • , Hanna M. Ollila
    • , Andrew R. Wood
    • , Vincent T. van Hees
    • , Ben Brumpton
    • , Bendik S. Winsvold
    • , Katri Kantojärvi
    • , Teemu Palviainen
    • , Brian E. Cade
    • , Tamar Sofer
    • , Yanwei Song
    • , Krunal Patel
    • , Simon G. Anderson
    • , David A. Bechtold
    • , Jack Bowden
    • , Richard Emsley
    • , Simon D. Kyle
    • , Max A. Little
    • , Andrew S. Loudon
    • , Frank A. J. L. Scheer
    • , Shaun M. Purcell
    • , Rebecca C. Richmond
    • , Kai Spiegelhalder
    • , Jessica Tyrrell
    • , Xiaofeng Zhu
    • , Christer Hublin
    • , Jaakko A. Kaprio
    • , Kati Kristiansson
    • , Sonja Sulkava
    • , Tiina Paunio
    • , Kristian Hveem
    • , Jonas B. Nielsen
    • , Cristen J. Willer
    • , John-Anker Zwart
    • , Linn B. Strand
    • , Timothy M. Frayling
    • , David Ray
    • , Deborah A. Lawlor
    • , Martin K. Rutter
    • , Michael N. Weedon
    • , Susan Redline
    •  & Richa Saxena
  • Article
    | Open Access

    Hsp chaperones stabilize the inactive conformation of androgen receptor (AR) and are released upon hormone-induced AR activation. Here, the authors locate the Hsp binding region on AR, and show that Hsp70 reduces AR aggregation and promotes AR degradation in cellular and mouse models of a neuromuscular disorder.

    • Bahareh Eftekharzadeh
    • , Varuna C. Banduseela
    • , Giulio Chiesa
    • , Paula Martínez-Cristóbal
    • , Jennifer N. Rauch
    • , Samir R. Nath
    • , Daniel M. C. Schwarz
    • , Hao Shao
    • , Marta Marin-Argany
    • , Claudio Di Sanza
    • , Elisa Giorgetti
    • , Zhigang Yu
    • , Roberta Pierattelli
    • , Isabella C. Felli
    • , Isabelle Brun-Heath
    • , Jesús García
    • , Ángel R. Nebreda
    • , Jason E. Gestwicki
    • , Andrew P. Lieberman
    •  & Xavier Salvatella
  • Article
    | Open Access

    Memory is hypothesised to depend on different brain regions that interact in a network. Here, the authors use case studies of stroke patients with amnesia from the literature to identify brain regions that are part of this network.

    • Michael A. Ferguson
    • , Chun Lim
    • , Danielle Cooke
    • , R. Ryan Darby
    • , Ona Wu
    • , Natalia S. Rost
    • , Maurizio Corbetta
    • , Jordan Grafman
    •  & Michael D. Fox
  • Article
    | Open Access

    Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

    • Xiaopu Zhou
    • , Yu Chen
    • , Kin Y. Mok
    • , Timothy C. Y. Kwok
    • , Vincent C. T. Mok
    • , Qihao Guo
    • , Fanny C. Ip
    • , Yuewen Chen
    • , Nandita Mullapudi
    • , Michael W. Weiner
    • , Paul Aisen
    • , Ronald Petersen
    • , Clifford R. Jack
    • , William Jagust
    • , John Q. Trojanowski
    • , Arthur W. Toga
    • , Laurel Beckett
    • , Robert C. Green
    • , Andrew J. Saykin
    • , John Morris
    • , Leslie M. Shaw
    • , Zaven Khachaturian
    • , Greg Sorensen
    • , Lew Kuller
    • , Marcus Raichle
    • , Steven Paul
    • , Peter Davies
    • , Howard Fillit
    • , Franz Hefti
    • , David Holtzman
    • , Marek M. Mesulam
    • , William Potter
    • , Peter Snyder
    • , Adam Schwartz
    • , Tom Montine
    • , Ronald G. Thomas
    • , Michael Donohue
    • , Sarah Walter
    • , Devon Gessert
    • , Tamie Sather
    • , Gus Jiminez
    • , Danielle Harvey
    • , Matthew Bernstein
    • , Paul Thompson
    • , Norbert Schuff
    • , Bret Borowski
    • , Jeff Gunter
    • , Matt Senjem
    • , Prashanthi Vemuri
    • , David Jones
    • , Kejal Kantarci
    • , Chad Ward
    • , Robert A. Koeppe
    • , Norm Foster
    • , Eric M. Reiman
    • , Kewei Chen
    • , Chet Mathis
    • , Susan Landau
    • , Nigel J. Cairns
    • , Erin Householder
    • , Lisa Taylor-Reinwald
    • , Virginia Lee
    • , Magdalena Korecka
    • , Michal Figurski
    • , Karen Crawford
    • , Scott Neu
    • , Tatiana M. Foroud
    • , Steven G. Potkin
    • , Li Shen
    • , Kelley Faber
    • , Sungeun Kim
    • , Kwangsik Nho
    • , Leon Thal
    • , Neil Buckholtz
    • , Marylyn Albert
    • , Richard Frank
    • , John Hsiao
    • , Jeffrey Kaye
    • , Joseph Quinn
    • , Betty Lind
    • , Raina Carter
    • , Sara Dolen
    • , Lon S. Schneider
    • , Sonia Pawluczyk
    • , Mauricio Beccera
    • , Liberty Teodoro
    • , Bryan M. Spann
    • , James Brewer
    • , Helen Vanderswag
    • , Adam Fleisher
    • , Judith L. Heidebrink
    • , Joanne L. Lord
    • , Sara S. Mason
    • , Colleen S. Albers
    • , David Knopman
    • , Kris Johnson
    • , Rachelle S. Doody
    • , Javier Villanueva-Meyer
    • , Munir Chowdhury
    • , Susan Rountree
    • , Mimi Dang
    • , Yaakov Stern
    • , Lawrence S. Honig
    • , Karen L. Bell
    • , Beau Ances
    • , Maria Carroll
    • , Sue Leon
    • , Mark A. Mintun
    • , Stacy Schneider
    • , Angela Oliver
    • , Daniel Marson
    • , Randall Griffith
    • , David Clark
    • , David Geldmacher
    • , John Brockington
    • , Erik Roberson
    • , Hillel Grossman
    • , Effie Mitsis
    • , Leyla de Toledo-Morrell
    • , Raj C. Shah
    • , Ranjan Duara
    • , Daniel Varon
    • , Maria T. Greig
    • , Peggy Roberts
    • , Chiadi Onyike
    • , Daniel D’Agostino
    • , Stephanie Kielb
    • , James E. Galvin
    • , Brittany Cerbone
    • , Christina A. Michel
    • , Henry Rusinek
    • , Mony J. de Leon
    • , Lidia Glodzik
    • , Susan De Santi
    • , P Murali Doraiswamy
    • , Jeffrey R. Petrella
    • , Terence Z. Wong
    • , Steven E. Arnold
    • , Jason H. Karlawish
    • , David Wolk
    • , Charles D. Smith
    • , Greg Jicha
    • , Peter Hardy
    • , Partha Sinha
    • , Elizabeth Oates
    • , Gary Conrad
    • , Oscar L. Lopez
    • , MaryAnn Oakley
    • , Donna M. Simpson
    • , Anton P. Porsteinsson
    • , Bonnie S. Goldstein
    • , Kim Martin
    • , Kelly M. Makino
    • , M Saleem Ismail
    • , Connie Brand
    • , Ruth A. Mulnard
    • , Gaby Thai
    • , Catherine McAdams-Ortiz
    • , Kyle Womack
    • , Dana Mathews
    • , Mary Quiceno
    • , Ramon Diaz-Arrastia
    • , Richard King
    • , Myron Weiner
    • , Kristen Martin-Cook
    • , Michael DeVous
    • , Allan I Levey
    • , James J. Lah
    • , Janet S. Cellar
    • , Jeffrey M. Burns
    • , Heather S. Anderson
    • , Russell H. Swerdlow
    • , Liana Apostolova
    • , Kathleen Tingus
    • , Ellen Woo
    • , Daniel H. S. Silverman
    • , Po H. Lu
    • , George Bartzokis
    • , Neill R. Graff-Radford
    • , Francine Parfitt
    • , Tracy Kendall
    • , Heather Johnson
    • , Martin R. Farlow
    • , Ann Marie Hake
    • , Brandy R. Matthews
    • , Scott Herring
    • , Cynthia Hunt
    • , Christopher H. van Dyck
    • , Richard E. Carson
    • , Martha G. MacAvoy
    • , Howard Chertkow
    • , Howard Bergman
    • , Chris Hosein
    • , Ging-Yuek Robin Hsiung
    • , Howard Feldman
    • , Benita Mudge
    • , Michele Assaly
    • , Charles Bernick
    • , Donna Munic
    • , Andrew Kertesz
    • , John Rogers
    • , Dick Trost
    • , Diana Kerwin
    • , Kristine Lipowski
    • , Chuang-Kuo Wu
    • , Nancy Johnson
    • , Carl Sadowsky
    • , Walter Martinez
    • , Teresa Villena
    • , Raymond Scott Turner
    • , Kathleen Johnson
    • , Brigid Reynolds
    • , Reisa A. Sperling
    • , Keith A. Johnson
    • , Gad Marshall
    • , Meghan Frey
    • , Barton Lane
    • , Allyson Rosen
    • , Jared Tinklenberg
    • , Marwan N. Sabbagh
    • , Christine M. Belden
    • , Sandra A. Jacobson
    • , Sherye A. Sirrel
    • , Neil Kowall
    • , Ronald Killiany
    • , Andrew E. Budson
    • , Alexander Norbash
    • , Patricia Lynn Johnson
    • , Joanne Allard
    • , Alan Lerner
    • , Paula Ogrocki
    • , Leon Hudson
    • , Evan Fletcher
    • , Owen Carmichael
    • , John Olichney
    • , Charles DeCarli
    • , Smita Kittur
    • , Michael Borrie
    • , T-Y. Lee
    • , Rob Bartha
    • , Sterling Johnson
    • , Sanjay Asthana
    • , Cynthia M. Carlsson
    • , Adrian Preda
    • , Dana Nguyen
    • , Pierre Tariot
    • , Stephanie Reeder
    • , Vernice Bates
    • , Horacio Capote
    • , Michelle Rainka
    • , Douglas W. Scharre
    • , Maria Kataki
    • , Anahita Adeli
    • , Earl A. Zimmerman
    • , Dzintra Celmins
    • , Alice D. Brown
    • , Godfrey D. Pearlson
    • , Karen Blank
    • , Karen Anderson
    • , Robert B. Santulli
    • , Tamar J. Kitzmiller
    • , Eben S. Schwartz
    • , Kaycee M. Sink
    • , Jeff D. Williamson
    • , Pradeep Garg
    • , Franklin Watkins
    • , Brian R. Ott
    • , Henry Querfurth
    • , Geoffrey Tremont
    • , Stephen Salloway
    • , Paul Malloy
    • , Stephen Correia
    • , Howard J. Rosen
    • , Bruce L. Miller
    • , Jacobo Mintzer
    • , Kenneth Spicer
    • , David Bachman
    • , Stephen Pasternak
    • , Irina Rachinsky
    • , Dick Drost
    • , Nunzio Pomara
    • , Raymundo Hernando
    • , Antero Sarrael
    • , Susan K. Schultz
    • , Laura L. Boles Ponto
    • , Hyungsub Shim
    • , Karen Elizabeth Smith
    • , Norman Relkin
    • , Gloria Chaing
    • , Lisa Raudin
    • , Amanda Smith
    • , Kristin Fargher
    • , Balebail Ashok Raj
    • , Thomas Neylan
    • , Jordan Grafman
    • , Melissa Davis
    • , Rosemary Morrison
    • , Jacqueline Hayes
    • , Shannon Finley
    • , Karl Friedl
    • , Debra Fleischman
    • , Konstantinos Arfanakis
    • , Olga James
    • , Dino Massoglia
    • , J Jay Fruehling
    • , Sandra Harding
    • , Elaine R. Peskind
    • , Eric C. Petrie
    • , Gail Li
    • , Jerome A. Yesavage
    • , Joy L. Taylor
    • , Ansgar J. Furst
    • , Paola Giusti-Rodríguez
    • , Patrick F. Sullivan
    • , John Hardy
    • , Amy K. Y. Fu
    • , Yun Li
    •  & Nancy Y. Ip
  • Article
    | Open Access

    Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca2+ transport and AMPAR currents.”

    • Vincenzo Salpietro
    • , Christine L. Dixon
    • , Hui Guo
    • , Oscar D. Bello
    • , Jana Vandrovcova
    • , Stephanie Efthymiou
    • , Reza Maroofian
    • , Gali Heimer
    • , Lydie Burglen
    • , Stephanie Valence
    • , Erin Torti
    • , Moritz Hacke
    • , Julia Rankin
    • , Huma Tariq
    • , Estelle Colin
    • , Vincent Procaccio
    • , Pasquale Striano
    • , Kshitij Mankad
    • , Andreas Lieb
    • , Sharon Chen
    • , Laura Pisani
    • , Conceicao Bettencourt
    • , Roope Männikkö
    • , Andreea Manole
    • , Alfredo Brusco
    • , Enrico Grosso
    • , Giovanni Battista Ferrero
    • , Judith Armstrong-Moron
    • , Sophie Gueden
    • , Omer Bar-Yosef
    • , Michal Tzadok
    • , Kristin G. Monaghan
    • , Teresa Santiago-Sim
    • , Richard E. Person
    • , Megan T. Cho
    • , Rebecca Willaert
    • , Yongjin Yoo
    • , Jong-Hee Chae
    • , Yingting Quan
    • , Huidan Wu
    • , Tianyun Wang
    • , Raphael A. Bernier
    • , Kun Xia
    • , Alyssa Blesson
    • , Mahim Jain
    • , Mohammad M. Motazacker
    • , Bregje Jaeger
    • , Amy L. Schneider
    • , Katja Boysen
    • , Alison M. Muir
    • , Candace T. Myers
    • , Ralitza H. Gavrilova
    • , Lauren Gunderson
    • , Laura Schultz-Rogers
    • , Eric W. Klee
    • , David Dyment
    • , Matthew Osmond
    • , Mara Parellada
    • , Cloe Llorente
    • , Javier Gonzalez-Peñas
    • , Angel Carracedo
    • , Arie Van Haeringen
    • , Claudia Ruivenkamp
    • , Caroline Nava
    • , Delphine Heron
    • , Rosaria Nardello
    • , Michele Iacomino
    • , Carlo Minetti
    • , Aldo Skabar
    • , Antonella Fabretto
    • , Michael G. Hanna
    • , Enrico Bugiardini
    • , Isabel Hostettler
    • , Benjamin O’Callaghan
    • , Alaa Khan
    • , Andrea Cortese
    • , Emer O’Connor
    • , Wai Y. Yau
    • , Thomas Bourinaris
    • , Rauan Kaiyrzhanov
    • , Viorica Chelban
    • , Monika Madej
    • , Maria C. Diana
    • , Maria S. Vari
    • , Marina Pedemonte
    • , Claudio Bruno
    • , Ganna Balagura
    • , Marcello Scala
    • , Chiara Fiorillo
    • , Lino Nobili
    • , Nancy T. Malintan
    • , Maria N. Zanetti
    • , Shyam S. Krishnakumar
    • , Gabriele Lignani
    • , James E. C. Jepson
    • , Paolo Broda
    • , Simona Baldassari
    • , Pia Rossi
    • , Floriana Fruscione
    • , Francesca Madia
    • , Monica Traverso
    • , Patrizia De-Marco
    • , Belen Pérez-Dueñas
    • , Francina Munell
    • , Yamna Kriouile
    • , Mohamed El-Khorassani
    • , Blagovesta Karashova
    • , Daniela Avdjieva
    • , Hadil Kathom
    • , Radka Tincheva
    • , Lionel Van-Maldergem
    • , Wolfgang Nachbauer
    • , Sylvia Boesch
    • , Antonella Gagliano
    • , Elisabetta Amadori
    • , Jatinder S. Goraya
    • , Tipu Sultan
    • , Salman Kirmani
    • , Shahnaz Ibrahim
    • , Farida Jan
    • , Jun Mine
    • , Selina Banu
    • , Pierangelo Veggiotti
    • , Gian V. Zuccotti
    • , Michel D. Ferrari
    • , Arn M. J. Van Den Maagdenberg
    • , Alberto Verrotti
    • , Gian L. Marseglia
    • , Salvatore Savasta
    • , Miguel A. Soler
    • , Carmela Scuderi
    • , Eugenia Borgione
    • , Roberto Chimenz
    • , Eloisa Gitto
    • , Valeria Dipasquale
    • , Alessia Sallemi
    • , Monica Fusco
    • , Caterina Cuppari
    • , Maria C. Cutrupi
    • , Martino Ruggieri
    • , Armando Cama
    • , Valeria Capra
    • , Niccolò E. Mencacci
    • , Richard Boles
    • , Neerja Gupta
    • , Madhulika Kabra
    • , Savvas Papacostas
    • , Eleni Zamba-Papanicolaou
    • , Efthymios Dardiotis
    • , Shazia Maqbool
    • , Nuzhat Rana
    • , Osama Atawneh
    • , Shen Y. Lim
    • , Farooq Shaikh
    • , George Koutsis
    • , Marianthi Breza
    • , Domenico A. Coviello
    • , Yves A. Dauvilliers
    • , Issam AlKhawaja
    • , Mariam AlKhawaja
    • , Fuad Al-Mutairi
    • , Tanya Stojkovic
    • , Veronica Ferrucci
    • , Massimo Zollo
    • , Fowzan S. Alkuraya
    • , Maria Kinali
    • , Hamed Sherifa
    • , Hanene Benrhouma
    • , Ilhem B. Y. Turki
    • , Meriem Tazir
    • , Makram Obeid
    • , Sophia Bakhtadze
    • , Nebal W. Saadi
    • , Maha S. Zaki
    • , Chahnez C. Triki
    • , Fabio Benfenati
    • , Stefano Gustincich
    • , Majdi Kara
    • , Vincenzo Belcastro
    • , Nicola Specchio
    • , Giuseppe Capovilla
    • , Ehsan G. Karimiani
    • , Ahmed M. Salih
    • , Njideka U. Okubadejo
    • , Oluwadamilola O. Ojo
    • , Olajumoke O. Oshinaike
    • , Olapeju Oguntunde
    • , Kolawole Wahab
    • , Abiodun H. Bello
    • , Sanni Abubakar
    • , Yahaya Obiabo
    • , Ernest Nwazor
    • , Oluchi Ekenze
    • , Uduak Williams
    • , Alagoma Iyagba
    • , Lolade Taiwo
    • , Morenikeji Komolafe
    • , Konstantin Senkevich
    • , Chingiz Shashkin
    • , Nazira Zharkynbekova
    • , Kairgali Koneyev
    • , Ganieva Manizha
    • , Maksud Isrofilov
    • , Ulviyya Guliyeva
    • , Kamran Salayev
    • , Samson Khachatryan
    • , Salvatore Rossi
    • , Gabriella Silvestri
    • , Nourelhoda Haridy
    • , Luca A. Ramenghi
    • , Georgia Xiromerisiou
    • , Emanuele David
    • , Mhammed Aguennouz
    • , Liana Fidani
    • , Cleanthe Spanaki
    • , Arianna Tucci
    • , Miquel Raspall-Chaure
    • , Michael Chez
    • , Anne Tsai
    • , Emily Fassi
    • , Marwan Shinawi
    • , John N. Constantino
    • , Rita De Zorzi
    • , Sara Fortuna
    • , Fernando Kok
    • , Boris Keren
    • , Dominique Bonneau
    • , Murim Choi
    • , Bruria Benzeev
    • , Federico Zara
    • , Heather C. Mefford
    • , Ingrid E. Scheffer
    • , Jill Clayton-Smith
    • , Alfons Macaya
    • , James E. Rothman
    • , Evan E. Eichler
    • , Dimitri M. Kullmann
    •  & Henry Houlden
  • Article
    | Open Access

    Advanced paternal age associates with increased risk for psychiatric and developmental disorders in offspring. Here, Taylor et al. utilize parent-child trio exome sequencing data sets to estimate the contribution of paternal age-related de novo mutations to multiple disorders, including heart disease and schizophrenia.

    • Jacob L. Taylor
    • , Jean-Christophe P. G. Debost
    • , Sarah U. Morton
    • , Emilie M. Wigdor
    • , Henrike O. Heyne
    • , Dennis Lal
    • , Daniel P. Howrigan
    • , Alex Bloemendal
    • , Janne T. Larsen
    • , Jack A. Kosmicki
    • , Daniel J. Weiner
    • , Jason Homsy
    • , Jonathan G. Seidman
    • , Christine E. Seidman
    • , Esben Agerbo
    • , John J. McGrath
    • , Preben Bo Mortensen
    • , Liselotte Petersen
    • , Mark J. Daly
    •  & Elise B. Robinson
  • Article
    | Open Access

    Depression and transient ischaemic attacks are tightly regulated but the neural circuits underlying depression-modulated ischaemic injury are not known. Here, the authors show that the locus coeruleus-CA1 pathway is involved in depression-associated ischaemia susceptibility.

    • Qian Zhang
    • , Dian Xing Hu
    • , Feng He
    • , Chun Yang Li
    • , Guang Jian Qi
    • , Hong Wei Cai
    • , Tong Xia Li
    • , Jie Ming
    • , Pei Zhang
    • , Xiao Qian Chen
    •  & Bo Tian
  • Article
    | Open Access

    The reticular activating system (RAS) of the brainstem regulates wakefulness, and stimulation of RAS areas can reverse effects of anaesthesia. Here, the authors show that stimulation of a particular RAS area, the anterior portion of nucleus gigantocellularis, can produce arousal from deep coma.

    • S. Gao
    • , A. Proekt
    • , N. Renier
    • , D. P. Calderon
    •  & D. W. Pfaff
  • Article
    | Open Access

    Amyloid-β (Aβ) deposition occurs in Alzheimer's disease but its relation to disease features such as local brain hypometabolism or cognitive decline is unclear. Here, the authors show that Aβ aggregation in the brain’s default mode network leads to hypometabolism in distant but functionally connected areas.

    • Tharick A. Pascoal
    • , Sulantha Mathotaarachchi
    • , Min Su Kang
    • , Sara Mohaddes
    • , Monica Shin
    • , Ah Yeon Park
    • , Maxime J. Parent
    • , Andrea L. Benedet
    • , Mira Chamoun
    • , Joseph Therriault
    • , Heungsun Hwang
    • , A. Claudio Cuello
    • , Bratislav Misic
    • , Jean-Paul Soucy
    • , John A. D. Aston
    • , Serge Gauthier
    •  & Pedro Rosa-Neto
  • Article
    | Open Access

    Genome-wide association studies (GWAS) have so far uncovered more than 200 loci for multiple sclerosis (MS). Here, the authors integrate data from various sources for a cell type-specific pathway analysis of MS GWAS results that specifically highlights the involvement of the immune system in disease pathogenesis.

    • Lohith Madireddy
    • , Nikolaos A. Patsopoulos
    • , Chris Cotsapas
    • , Steffan D. Bos
    • , Ashley Beecham
    • , Jacob McCauley
    • , Kicheol Kim
    • , Xiaoming Jia
    • , Adam Santaniello
    • , Stacy J. Caillier
    • , Till F. M. Andlauer
    • , Lisa F. Barcellos
    • , Tone Berge
    • , Luisa Bernardinelli
    • , Filippo Martinelli-Boneschi
    • , David R. Booth
    • , Farren Briggs
    • , Elisabeth G. Celius
    • , Manuel Comabella
    • , Giancarlo Comi
    • , Bruce A. C. Cree
    • , Sandra D’Alfonso
    • , Katrina Dedham
    • , Pierre Duquette
    • , Efthimios Dardiotis
    • , Federica Esposito
    • , Bertrand Fontaine
    • , Christiane Gasperi
    • , An Goris
    • , Bénédicte Dubois
    • , Pierre-Antoine Gourraud
    • , Georgios Hadjigeorgiou
    • , Jonathan Haines
    • , Clive Hawkins
    • , Bernhard Hemmer
    • , Rogier Hintzen
    • , Dana Horakova
    • , Noriko Isobe
    • , Seema Kalra
    • , Jun-ichi Kira
    • , Michael Khalil
    • , Ingrid Kockum
    • , Christina M. Lill
    • , Matthew R. Lincoln
    • , Felix Luessi
    • , Roland Martin
    • , Annette Oturai
    • , Aarno Palotie
    • , Margaret A. Pericak-Vance
    • , Roland Henry
    • , Janna Saarela
    • , Adrian Ivinson
    • , Tomas Olsson
    • , Bruce V. Taylor
    • , Graeme J. Stewart
    • , Hanne F. Harbo
    • , Alastair Compston
    • , Stephen L. Hauser
    • , David A. Hafler
    • , Frauke Zipp
    • , Philip De Jager
    • , Stephen Sawcer
    • , Jorge R. Oksenberg
    •  & Sergio E. Baranzini
  • Article
    | Open Access

    Convolutional neural networks have been applied to various areas of medical imaging and histology. Here the authors develop an automated approach using interpretable neural networks to determine Alzheimer’s disease plaque and cerebral amyloid angiopathy burden in post-mortem human brain tissue.

    • Ziqi Tang
    • , Kangway V. Chuang
    • , Charles DeCarli
    • , Lee-Way Jin
    • , Laurel Beckett
    • , Michael J. Keiser
    •  & Brittany N. Dugger
  • Article
    | Open Access

    A key challenge is to find/re-purpose approved drugs that could be used in humans to induce autophagy-associated clearance of neurodegenerative proteins. Here, authors demonstrate that felodipine, an anti-hypertensive drug, can induce autophagy and clear a variety of aggregated neurodegenerative disease-associated proteins in mouse brains at plasma concentrations similar to those that would be seen in humans taking the drug.

    • Farah H. Siddiqi
    • , Fiona M. Menzies
    • , Ana Lopez
    • , Eleanna Stamatakou
    • , Cansu Karabiyik
    • , Rodrigo Ureshino
    • , Thomas Ricketts
    • , Maria Jimenez-Sanchez
    • , Miguel Angel Esteban
    • , Liangxue Lai
    • , Micky D. Tortorella
    • , Zhiwei Luo
    • , Hao Liu
    • , Emmanouil Metzakopian
    • , Hugo J. R. Fernandes
    • , Andrew Bassett
    • , Eric Karran
    • , Bruce L. Miller
    • , Angeleen Fleming
    •  & David C. Rubinsztein
  • Article
    | Open Access

    Diagnosis and classification of peripheral neuropathy (PN) is facilitated by nerve conduction (NC) studies. Here, Bjornsdottir et al. find a low-frequency PRPH splice-donor variant that associates with NC amplitude and neurological assessment of recalled PRPH variant carriers reveals increased risk of a mild sensory-negative PN.

    • Gyda Bjornsdottir
    • , Erna V. Ivarsdottir
    • , Kristbjorg Bjarnadottir
    • , Stefania Benonisdottir
    • , Sandra Sif Gylfadottir
    • , Gudny A. Arnadottir
    • , Rafn Benediktsson
    • , Gisli Hreinn Halldorsson
    • , Anna Helgadottir
    • , Adalbjorg Jonasdottir
    • , Aslaug Jonasdottir
    • , Ingileif Jonsdottir
    • , Anna Margret Kristinsdottir
    • , Olafur Th. Magnusson
    • , Gisli Masson
    • , Pall Melsted
    • , Thorunn Rafnar
    • , Asgeir Sigurdsson
    • , Gunnar Sigurdsson
    • , Astros Skuladottir
    • , Valgerdur Steinthorsdottir
    • , Unnur Styrkarsdottir
    • , Gudmundur Thorgeirsson
    • , Gudmar Thorleifsson
    • , Arnor Vikingsson
    • , Daniel F. Gudbjartsson
    • , Hilma Holm
    • , Hreinn Stefansson
    • , Unnur Thorsteinsdottir
    • , Gudmundur L. Norddahl
    • , Patrick Sulem
    • , Thorgeir E. Thorgeirsson
    •  & Kari Stefansson
  • Article
    | Open Access

    Onion bulbs are a hallmark of demyelinating peripheral neuropathies. Here the authors identify Neuregulin-1 type I expression in Schwann cells as an essential mechanism involved in the formation of these characteristic structures.

    • Robert Fledrich
    • , Dagmar Akkermann
    • , Vlad Schütza
    • , Tamer A. Abdelaal
    • , Doris Hermes
    • , Erik Schäffner
    • , M. Clara Soto-Bernardini
    • , Tilmann Götze
    • , Axel Klink
    • , Kathrin Kusch
    • , Martin Krueger
    • , Theresa Kungl
    • , Clara Frydrychowicz
    • , Wiebke Möbius
    • , Wolfgang Brück
    • , Wolf C. Mueller
    • , Ingo Bechmann
    • , Michael W. Sereda
    • , Markus H. Schwab
    • , Klaus-Armin Nave
    •  & Ruth M. Stassart