Featured
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Article
| Open Access
Ancestral allele of DNA polymerase gamma modifies antiviral tolerance
The POLG1 mutation p.W748S, which is associated with mitochondrial recessive ataxia syndrome, dampens innate immune responses by compromising mtDNA replisome stability, and this explains why a viral infection can trigger the development of the disease and contribute to its variable clinical manifestation.
- Yilin Kang
- , Jussi Hepojoki
- & Anu Suomalainen
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Research Briefing |
Dysregulated cellular stress management becomes a source of stress
Stress responses protect cells from harmful conditions, but once the stress has resolved, these responses must be actively turned off to avoid cell damage that might lead to the development of neurodegenerative disease.
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News & Views |
Non-neuronal brain cells modulate behaviour
A single gene in astrocytes can constrain repetitive behaviours, indicating that these cells are regulators of behavioural disruption in conditions such as Huntington’s disease and obsessive–compulsive disorder.
- Anna Kruyer
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News & Views |
Synchronized neuronal activity drives waste fluid flow
Active neurons can stimulate the clearance of their own metabolic waste by driving changes to ion gradients in the surrounding fluid and by promoting the pulsation of nearby blood vessels.
- Lauren Hablitz
- & Maiken Nedergaard
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Article
| 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
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News |
Early dementia diagnosis: blood proteins reveal at-risk people
The results of a large-scale screening study could be used to develop blood tests to diagnose diseases such as Alzheimer’s before symptoms take hold.
- Miryam Naddaf
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News |
Signs of ‘transmissible’ Alzheimer’s seen in people who received growth hormone
The findings support a controversial hypothesis that proteins related to the neurodegenerative disease can be ‘seeded’ in the brain through material taken from cadavers.
- Carissa Wong
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News |
Obesity drugs have another superpower: taming inflammation
The blockbuster medications that reduce body weight also reduce inflammation in organs such as the brain, raising hopes that they can treat Parkinson's and Alzheimer's diseases.
- Mariana Lenharo
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News |
Ancient DNA reveals origins of multiple sclerosis in Europe
A huge cache of ancient genomes spanning tens of thousands of years reveals the roots of traits in modern Europeans.
- Sara Reardon
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News |
Potent psychedelic drug banishes PTSD, small study finds
Military veterans with cognitive and psychological problems saw drastic improvements after a dose of ibogaine.
- Max Kozlov
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Article
| Open Access
TAF15 amyloid filaments in frontotemporal lobar degeneration
Cryogenic electron microscopy structures of amyloid filaments extracted from patient brains reveal that the protein TAF15 forms filaments that characterize certain cases of frontotemporal lobar degeneration.
- Stephan Tetter
- , Diana Arseni
- & Benjamin Ryskeldi-Falcon
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Article
| Open Access
m1A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration
TDP-43 binds to N1-methyladenosine on CAG repeat RNA, resulting in the formation of gel-like TDP-43 aggregates in the cytoplasm that resemble those observed in neurological disease pathology.
- Yuxiang Sun
- , Hui Dai
- & Yinsheng Wang
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News |
Spinal implant helps man with advanced Parkinson’s to walk without falling
Electrical stimulation improved his mobility, although researchers say that a larger study is needed to assess the device.
- Emily Waltz
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News |
The brain cells linked to protection against dementia
People with an abundance of specific neurons are more likely to escape cognitive decline despite having signs of Alzheimer’s in their brains.
- Sara Reardon
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News & Views |
How the cGAS–STING system links inflammation and cognitive decline
When DNA is misplaced inside cells, the cGAS–STING molecular system triggers inflammation. It emerges that stimulation of this mechanism in microglial cells of the brain during ageing contributes to cognitive decline.
- Bart J. L. Eggen
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Article
| Open Access
TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP
Cryo-electron microscopy structures and mass spectrometry analyses show that TAR DNA-binding protein 43 (TDP-43) forms amyloid filaments with a distinct fold in type A frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP) compared with TDP-43 filaments in type B FTLD-TDP and amyotrophic lateral sclerosis.
- Diana Arseni
- , Renren Chen
- & Benjamin Ryskeldi-Falcon
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News |
Alzheimer’s drug donanemab helps most when taken at earliest disease stage, study finds
But the drug, an antibody that attacks the protein amyloid, does not work as well in people with more advanced disease.
- Sara Reardon
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News |
Anti-ageing protein injection boosts monkeys’ memories
First primate studies to show cognitive benefits of the protein klotho could be a step towards clinical applications.
- Lilly Tozer
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News |
Does shingles vaccination cut dementia risk? Large study hints at a link
Analysis of nearly 300,000 people finds an association between the shingles jab and a lower rate of dementia — but questions linger.
- Sara Reardon
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Article
| Open Access
Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy
The membrane-shaping protein ARL6IP1 is involved in the selective degradation of the endoplasmic reticulum, and this process depends on its ubiquitination and interaction with other membrane-shaping proteins such as FAM134B.
- Hector Foronda
- , Yangxue Fu
- & Christian A. Hübner
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Technology Feature |
Brain imaging: fMRI advances make scans sharper and faster
Researchers are finding ways to improve one of neuroscientists’ favourite tools: functional magnetic resonance imaging.
- Diana Kwon
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News & Views |
Activated immune cells drive neurodegeneration in an Alzheimer’s model
An analysis of mice carrying the protein tau — a hallmark of Alzheimer’s disease — reveals that immune cells collaborate to drive tau-mediated neurodegeneration, and that drugs already in use in the clinic can combat this decline.
- Ian H. Guldner
- & Tony Wyss-Coray
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Article |
Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy
A study finds T cells in areas of tau, not amyloid, pathology in Alzheimer’s disease brain and mouse models, with their presence correlating with neuronal loss and their depletion, or that of microglia, preventing neurodegeneration and cognitive decline.
- Xiaoying Chen
- , Maria Firulyova
- & David M. Holtzman
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News & Views |
Drug trial for Alzheimer’s disease is a game changer
An antibody treatment reduces measurements of brain abnormalities called amyloid plaques in people with Alzheimer’s disease, and lessens clinical decline. This result will help in developing therapies to treat and prevent the disease.
- Eric M. Reiman
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News & Views |
The Alzheimer’s risk gene APOE modulates the gut–brain axis
Signals from gut microorganisms to the brain might be involved in neurodegeneration. It emerges that the gene APOE — variants of which each confer a different risk of Alzheimer’s disease — has a role in modulating this gut–brain communication.
- Alfonso Martín-Peña
- & Malú Gámez Tansey
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Research Highlight |
Link between brain atrophy and the microbiome emerges in mice
Changes similar to those seen in Alzheimer’s disease are less pronounced in mice with minimal levels of gut bacteria.
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Article
| Open Access
Medin co-aggregates with vascular amyloid-β in Alzheimer’s disease
Medin promotes the formation of vascular aggregates with amyloid-β in mouse models and in human patients with Alzheimer’s disease, and is associated with vascular defects and cognitive decline.
- Jessica Wagner
- , Karoline Degenhardt
- & Jonas J. Neher
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Article |
Structures of α-synuclein filaments from human brains with Lewy pathology
The authors report on the structures of α-synuclein filaments from the brains of individuals with Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies and how they differ from those seen in multiple system atrophy.
- Yang Yang
- , Yang Shi
- & Michel Goedert
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Research Briefing |
Tracing the brain circuitry underlying movement and mood symptoms in Parkinson’s disease
Parkinson’s disease causes slowness of movement, tremor and stiffness, along with mood symptoms such as depression. The brain’s parafascicular thalamus is shown to contain distinct neural circuits for locomotion, motor learning and depression-like states, and targeting these circuits alleviates some deficits in a mouse model of the disease.
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Article |
Divergent transcriptional regulation of astrocyte reactivity across disorders
Transcriptional changes associated with astrocyte reactivity are highly heterogeneous and are customized from vast numbers of potential DEGs through context-specific combinatorial interactions amongst transcriptional regulators.
- Joshua E. Burda
- , Timothy M. O’Shea
- & Michael V. Sofroniew
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News |
Young brain fluid improves memory in old mice
A protein in cerebrospinal fluid helps boost cells that maintain brain function.
- Jude Coleman
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News & Views |
An unexpected protein aggregate in diseased and ageing brains
Protein fibrils accumulate in the brain during neurodegeneration. Cryo-electron microscopy has now uncovered fibrils of a protein not previously thought to accumulate.
- Hideyuki Takahashi
- & Stephen M. Strittmatter
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News Feature |
Could drugs prevent Alzheimer’s? These trials aim to find out
Researchers are giving drugs to healthy people in hope of clearing away toxic proteins in the brain and warding off neurodegeneration.
- Alison Abbott
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News & Views |
Mechanism underlying a risk gene in neurodegeneration
Messenger RNA from the gene UNC13A is misprocessed in people who have neurodegenerative diseases known as ALS and FTD. The discovery could explain the disease risk associated with variants in this gene.
- Noa Lipstein
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Article
| Open Access
TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A
Risk variants for ALS and FTD in the synaptic gene UNC13A increase the expression of an UNC13A cryptic exon in neurons with TDP-43 depletion.
- Anna-Leigh Brown
- , Oscar G. Wilkins
- & Pietro Fratta
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Article
| Open Access
TDP-43 represses cryptic exon inclusion in the FTD–ALS gene UNC13A
TDP-43 controls an exon splicing event in UNC13A that results in the inclusion of a cryptic exon associated with frontotemporal dementia and amyotrophic lateral sclerosis.
- X. Rosa Ma
- , Mercedes Prudencio
- & Aaron D. Gitler
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Article |
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
A method called vessel isolation and nuclei extraction for sequencing (VINE-seq) produces a molecular map of vascular and perivascular cell types in the human brain and reveals their contributions to Alzheimer’s disease risk.
- Andrew C. Yang
- , Ryan T. Vest
- & Tony Wyss-Coray
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News & Views |
Aggregates of TDP-43 protein spiral into view
In some neurodegenerative diseases, a protein called TDP-43 forms aggregates in the brain, resulting in neuronal cell death. The structure of these aggregates and their properties have been unveiled.
- Hana M. Odeh
- & James Shorter
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Article |
Structure of pathological TDP-43 filaments from ALS with FTLD
Cryo-electron microscopy of aggregated TDP-43 from postmortem brain tissue of individuals who had ALS with FTLD reveals a filament structure with distinct features to other neuropathological protein filaments, such as those of tau and α-synuclein.
- Diana Arseni
- , Masato Hasegawa
- & Benjamin Ryskeldi-Falcon
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News Explainer |
More Alzheimer’s drugs head for FDA review: what scientists are watching
Eli Lilly and other pharma firms have begun submitting their anti-amyloid drug hopefuls for approval. But questions linger over the controversial precedent set by Biogen’s aducanumab.
- Asher Mullard
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News & Views |
Mice with disrupted mitochondria used to model Parkinson’s disease
Mice in which organelles called mitochondria are disrupted in vulnerable neuronal cells provide a new model of Parkinson’s disease. The pattern of neurodegeneration challenges long-held ideas about the disease’s motor symptoms.
- Zak Doric
- & Ken Nakamura
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Article |
Neurotoxic reactive astrocytes induce cell death via saturated lipids
Astrocytes can respond to diseases and injuries of the central nervous system by driving the death of neurons and mature oligodendrocytes through the delivery of long-chain saturated fatty acids contained in lipoparticles.
- Kevin A. Guttenplan
- , Maya K. Weigel
- & Ben A. Barres
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News & Views |
Structural strains of misfolded tau protein define different diseases
In diseases called tauopathies, misfolded tau proteins form aggregates called fibrils. Fibrils from nine different tauopathies show that tau misfolds in many ways, enabling the diseases to be classified according to fibril structure.
- Henning Stahlberg
- & Roland Riek
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Article |
Structure-based classification of tauopathies
Cryo-electron microscopy structures of tau filaments from progressive supranuclear palsy and other tauopathies reveal new filament conformations, and suggest that tauopathies can be classified on several different levels according to their filament folds.
- Yang Shi
- , Wenjuan Zhang
- & Sjors H. W. Scheres
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News & Views |
A protective signal between the brain’s supporting cells in Alzheimer’s disease
In a mouse model of Alzheimer’s disease, interleukin-3 protein released by cells called astrocytes activates microglia, the immune cells of the brain. These then cluster around disease-associated protein aggregates and help to clear them.
- Jerika J. Barron
- & Anna V. Molofsky
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Article |
Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease
Interleukin-3 signalling from astrocytes to microglia readies microglia to defend against Alzheimer’s disease.
- Cameron S. McAlpine
- , Joseph Park
- & Filip K. Swirski
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News |
Controversial Alzheimer’s drug approval could affect other diseases
Aducanumab’s fast-tracking has researchers both worried and hopeful about the future of drugs for neurodegenerative diseases such as Huntington’s and Parkinson’s.
- Asher Mullard
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News |
Failure of genetic therapies for Huntington’s devastates community
Hopes were high for drugs designed to lower levels of a mutant protein, but development has stalled.
- Diana Kwon
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News Feature |
Genetic therapies offer new hope against incurable brain diseases
A class of drugs that silence the effects of faulty genes could help tackle brain diseases — but a halted clinical trial has brought the field up short.
- Diana Kwon
Diabetes drug slows development of Parkinson’s disease