Neurodegenerative diseases

Article
14 February 2024 | Open Access

A model of human neural networks reveals NPTX2 pathology in ALS and FTLD

A neural stem cell culture system derived from induced pluripotent stem cells forms a network of synaptically connected and electrophysiologically active neurons that were used as a model system to identify a mechanism of TDP-43-induced neurodegeneration.

Marian Hruska-Plochan
, Vera I. Wiersma
& Magdalini Polymenidou

Article | 28 March 2022

Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43

Amyloid fibrils extracted from brains of patients with frontotemporal lobar degeneration with TAR DNA-binding-protein immunoreactivity (FTLD-TDP) are made up of transmembrane protein 106B.

Yi Xiao Jiang
, Qin Cao
& David S. Eisenberg

Article | 29 January 2020

ATP13A2 deficiency disrupts lysosomal polyamine export

The lysosomal polyamine transporter ATP13A2 controls the cellular polyamine content, and impaired lysosomal polyamine export represents a lysosome-dependent cell death pathway that may be implicated in ATP13A2-associated neurodegeneration.

Sarah van Veen
, Shaun Martin
& Peter Vangheluwe

Article | 20 November 2019

NLRP3 inflammasome activation drives tau pathology

The authors show that NLRP3 inflammasome is activated in microglia of patients with fronto-temporal dementia and in a mouse model of tau pathology, and that the loss of NLRP3 inflammasome function decreases tau pathology and improves cognition in mice.

Christina Ising
, Carmen Venegas
& Michael T. Heneka

Letter | 13 December 2018

Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone

Archived vials of cadaveric human growth hormone contain substantial levels of amyloid-β (Aβ) peptides and can seed Aβ plaques in susceptible mice, suggesting that this material could have transmitted Aβ pathology to humans.

Silvia A. Purro
, Mark A. Farrow
& John Collinge

Article | 21 December 2017

Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease

Deposition and spreading of amyloid-β pathology in mice requires binding to microglia-released ASC specks.

Carmen Venegas
, Sathish Kumar
& Michael T. Heneka

Letter | 30 August 2017

A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease

Braf ^V600E expression in resident macrophage progenitors leads to clonal expansion of ERK-activated microglia, which causes synaptic and neuronal loss in the brain and results in lethal neurodegenerative disease in adult mice.

Elvira Mass
, Christian E. Jacome-Galarza
& Frederic Geissmann

Letter | 12 April 2017

Antisense oligonucleotide therapy for spinocerebellar ataxia type 2

Antisense oligonucleotides against ATXN2 improved motor neuron function and restored firing frequency in cerebellar Purkinje cells in mouse models of spinocerebellar ataxia type 2.

Daniel R. Scoles
, Pratap Meera
& Stefan M. Pulst

Letter | 04 January 2017

Structural variation in amyloid-β fibrils from Alzheimer's disease clinical subtypes

Structural differences in 40- and 42-residue-long amyloid-β fibrils seeded in vitro from the cortical tissue of patients with different clinical subtypes of Alzheimer’s disease suggest that different fibril structures form in different disease variants and with different peptide lengths.

Wei Qiang
, Wai-Ming Yau
& Robert Tycko

Letter | 09 September 2015

Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

Treatment of children with human cadaver-derived growth hormone (c-hGH) contaminated with prions resulted in transmission of Creutzfeldt–Jakob disease (CJD); unexpectedly, in an autopsy study of eight such iCJD patients, the authors found amyloid-β deposition in the grey matter typical of that seen in Alzheimer's disease and amyloid-β in the blood vessel walls characteristic of cerebral amyloid angiopathy, consistent with iatrogenic transmission of amyloid-β pathology in addition to CJD and suggests that healthy c-hGH-exposed individuals may also be at risk of Alzheimer's disease and cerebral amyloid angiopathy.

Zane Jaunmuktane
, Simon Mead
& Sebastian Brandner

Letter | 26 August 2015

GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport

An unbiased genetic screen in Drosophila expressing G₄C₂-repeat-containing transcripts (repeats that in human cause pathogenesis in C9orf72-related neurological disease) finds genes that encode components of the nuclear pore and nucleocytoplasmic transport machinery, and reveals that G₄C₂ expanded-repeat-induced alterations in nucleocytoplasmic transport contribute to C9orf72 pathology and neurodegeneration.

Brian D. Freibaum
, Yubing Lu
& J. Paul Taylor

Brief Communications Arising | 01 April 2015

PLD3 and sporadic Alzheimer's disease risk

Jean-Charles Lambert
, Benjamin Grenier-Boley
& Philippe Amouyel

Brief Communications Arising | 01 April 2015

PLD3 variants in population studies

Sven J. van der Lee
, Henne Holstege
& Cornelia M. van Duijn

Brief Communications Arising | 01 April 2015

Cruchaga & Goate reply

Carlos Cruchaga
& Alison M. Goate

Brief Communications Arising | 01 April 2015

PLD3 in non-familial Alzheimer's disease

Stefanie Heilmann
, Dmitriy Drichel
& Alfredo Ramirez

Outlook | 22 May 2013

Neurodegeneration: Amyloid awakenings

Sleep disturbances may be an early sign of neurodegenerative diseases — but could sleep deficits cause these conditions in the first place?

Moheb Costandi

Article | 19 December 2012

Structure of a presenilin family intramembrane aspartate protease

Presenilin, the catalytic component of γ-secretase, cleaves amyloid precursor protein into short peptides that form the plaques that are found in the brains of patients with Alzheimer’s disease; here the structure of a presenilin homologue is described, which will serve as a framework for understanding the mechanisms of action of presenilin and γ-secretase.

Xiaochun Li
, Shangyu Dang
& Yigong Shi

News | 18 December 2012

Alzheimer’s test may undermine drug trials

Criteria used to assess cognitive function in the disease may not pick up subtle improvements.

Daniel Cressey

News | 09 December 2012

Brain cells made from urine

Human excreta could be a powerful source of cells to study disease, bypassing some of the problems of using stem cells.

Monya Baker

Research Highlights | 21 November 2012

Parkinson's protein spreads

News | 15 November 2012

Misfolded protein transmits Parkinson’s from cell to cell

Link between cell death and protein clumps opens pathway to possible treatment.

Virginia Hughes

Letter | 21 October 2012

Structural insight into the type-II mitochondrial NADH dehydrogenases

Analysis of the respective crystal structures of the yeast single-component type-II NADH dehydrogenase Ndi1 in its substrate-free form and when bound to NADH, ubiquinone and NADH–ubiquinone shows that Ndi1 homodimerization through its carboxy-terminal domain is critical for its catalytic activity and membrane targeting.

Yue Feng
, Wenfei Li
& Maojun Yang

News | 18 October 2012

Disrupted sleep may predict Alzheimer’s

Poor sleep patterns linked to formation of Alzheimer's plaques.

Mo Costandi

Letter | 17 October 2012

Progressive degeneration of human neural stem cells caused by pathogenic LRRK2

Investigation of neural cells from post-mortem human brains and differentiated from patient-derived induced pluripotent stem cells shows that the LRRK2 mutation (G2019S) associated with familial and sporadic Parkinson's disease correlates with abnormalities at the nuclear envelope.

Guang-Hui Liu
, Jing Qu
& Juan Carlos Izpisua Belmonte

News | 04 September 2012

Alzheimer’s drugs take a new tack

Hopes pinned on pre-emptive clinical trials after latest setbacks.

Ewen Callaway

News & Views | 01 August 2012

A protective mutation

A rare gene variant has been found that decreases the peptide deposition seen in the brains of people with Alzheimer's disease. The mutation may also slow the normal cognitive decline that occurs with age. See Letter p.96

Bart De Strooper
& Thierry Voet

Letter | 01 August 2012

Targeting nuclear RNA for in vivo correction of myotonic dystrophy

Nuclear-retained transcripts containing expanded repeats are shown to be sensitive to antisense silencing, and in a transgenic mouse model of myotonic dystrophy type 1, systemic administration of ASOs causes a rapid knockdown of the toxic RNA in skeletal muscle, correcting some hallmark features of the disease.

Thurman M. Wheeler
, Andrew J. Leger
& Charles A. Thornton

News | 11 July 2012

Gene mutation defends against Alzheimer’s disease

Rare genetic variant suggests a cause and treatment for cognitive decline.

Ewen Callaway

News & Views | 23 May 2012

A breach in the blood–brain barrier

Alterations in brain blood vessels in mice precede the neural dysfunction associated with Alzheimer's disease. The finding highlights potential targets for drug development. See Letter p.512

Peter Carmeliet
& Bart De Strooper

News | 22 May 2012

US government sets out Alzheimer’s plan

Health-agency budget windfall includes funding for two promising clinical trials.

Meredith Wadman

Letter | 16 May 2012

Apolipoprotein E controls cerebrovascular integrity via cyclophilin A

The APOE4-mediated proinflammatory pathway is shown to initiate blood–brain barrier breakdown and resulting neurodegeneration in transgenic mice.

Robert D. Bell
, Ethan A. Winkler
& Berislav V. Zlokovic

Letter | 06 May 2012

Sustained translational repression by eIF2α-P mediates prion neurodegeneration

Accumulation of prion protein during prion replication causes persistent translational repression of global protein synthesis, which is mediated by eIF2α-P and is associated with synaptic failure and neuronal loss in prion-diseased mice; promoting translational recovery in hippocampi of prion-infected mice is neuroprotective.

Julie A. Moreno
, Helois Radford
& Giovanna R. Mallucci

News | 02 May 2012

Eli Lilly freshens focus on neuroscience

New building for UK site bucks industry trends.

Daniel Cressey

Letter | 02 May 2012

Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β

It is shown that the formation of amyloid-β oligomers, one of the histopathological signatures of Alzheimer’s disease, can be triggered by small quantities of a specifically truncated and post-translationally modified version of amyloid-β.

Justin M. Nussbaum
, Stephan Schilling
& George S. Bloom

News | 18 March 2012

Bone-marrow transplant reverses Rett syndrome in mice

Rare autism spectrum disorder is partially caused by faulty immune cells in the brain.

Ewen Callaway

Letter | 29 February 2012

An epigenetic blockade of cognitive functions in the neurodegenerating brain

Histone deacetylase 2 is shown to suppress genes involved in cognitive function epigenetically, potentially opening the door to treatments for Alzheimer’s and other neurodegenerative diseases by developing HDAC2-selective inhibitors.

Johannes Gräff
, Damien Rei
& Li-Huei Tsai

News Explainer | 20 February 2012

Mystery US outbreak prompts further tests

Tourette’s-like disorder in New York school confounds experts.

Alison Motluk

News Feature | 15 February 2012

Prions and chaperones: Outside the fold

Susan Lindquist has challenged conventional thinking on how misfolded proteins drive disease and may power evolution. But she still finds that criticism stings.

Bijal P. Trivedi

News | 07 February 2012

Europe experiments with joined-up research

First Joint Programme announces its research strategy.

Alison Abbott

Letter | 25 January 2012

Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells

Induced pluripotent stem cells are shown to be useful for studying phenotypes relevant to familial and sporadic Alzheimer’s disease, even though it can take decades for the disease to manifest in patients.

Mason A. Israel
, Shauna H. Yuan
& Lawrence S. B. Goldstein

Research Highlights | 23 November 2011

Stress speeds up brain degeneration

Letter | 23 November 2011

Excitation-induced ataxin-3 aggregation in neurons from patients with Machado–Joseph disease

Human neurons derived from induced pluripotent stem cells permit the study of aberrant protein processing and aggregation in Machado–Joseph disease.

Philipp Koch
, Peter Breuer
& Oliver Brüstle

News | 21 November 2011

Host neurons obey transplants

Neurons derived from human embryonic stem cells can control native neurons in mice.

Charlotte Schubert

Letter | 06 November 2011

Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease

A new strategy for derivation of human midbrain dopamine neurons from pluripotent cells was developed; transplantation of the neurons in mice, rats and parkinsonian monkeys show they are a promising source of cells for applications in regenerative medicine.