Neurology

  • Article
    | Open Access

    Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive dementia. No clinical blood tests are available for diagnosis. The authors identified three miRNAs in whole-blood that are downregulated in sCJD patients, and discriminate sCJD from Alzheimer’s disease patients and healthy controls.

    • Penny J. Norsworthy
    • , Andrew G. B. Thompson
    •  & Emmanuelle A. Viré
  • Article
    | Open Access

    High resolution intravascular imaging in the brain is limited by the high tortuosity of the vasculature. Here the authors present a fiber optic imaging technology using high-frequency optical coherence tomography (HF-OCT) to provide volumetric high resolution images in the highly tortuous cerebral vasculature.

    • Giovanni J. Ughi
    • , Miklos G. Marosfoi
    •  & Ajit S. Puri
  • Article
    | Open Access

    Adeno-associated viruses (AAVs) are vehicles for gene therapy in humans, but currently only a limited amount of AAV serotypes is available. Here, the authors identify a novel AAV, AAVv66, and demonstrate enhanced production yields, virion stability, and CNS transduction compared to the clinically approved serotype AAV2.

    • Hung-Lun Hsu
    • , Alexander Brown
    •  & Guangping Gao
  • Article
    | Open Access

    Type I IFN has apposing effects in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Here the authors perform molecular profiling of NMOSD patients and mouse mechanistic experiments of neuro-inflammation to show that IFN-I stimulates pathogenic Th17 via IL-6 production by B cells.

    • Agnieshka M. Agasing
    • , Qi Wu
    •  & Robert C. Axtell
  • 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
    •  & 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
    •  & 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
    •  & Matthew. A. Lambon Ralph
  • 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
    •  & Brian J. Bacskai
  • 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
    •  & 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
    •  & Zhong Chen
  • 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
    •  & 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
    •  & 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
    •  & Johan N. Lundström
  • 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

    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
    •  & 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
    •  & 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
    •  & 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
    •  & Markus Zweckstetter
  • 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
    •  & 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
    •  & 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
    •  & Brad E. Zacharia
  • 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & 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
    •  & Elise B. Robinson
  • 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
    •  & Pedro Rosa-Neto