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Control of neuronal excitation–inhibition balance by BMP–SMAD1 signalling
Signalling by the developmental morphogen BMP2 through the transcription factor SMAD1 has a key role in controlling the glutamatergic innervation of parvalbumin-expressing interneurons and maintaining the balance between excitation and inhibition in the mammalian cortex.
- Zeynep Okur
- , Nadia Schlauri
- & Peter Scheiffele
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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 Highlight |
A test for Alzheimer’s-disease stage predicts dementia risk
Levels of a host of molecules in the cerebrospinal fluid reliably assess development of the disease.
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Article |
Disease-associated astrocyte epigenetic memory promotes CNS pathology
In an experimental autoimmune encephalomyelitis model in mice, a subset of astrocytes retains an epigenetically regulated memory of past inflammation, causing exacerbated inflammation upon subsequent rechallenge.
- Hong-Gyun Lee
- , Joseph M. Rone
- & Francisco J. Quintana
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Nature Index |
Researchers call for a major rethink of how Alzheimer’s treatments are evaluated
An approach that aims to quantify how long a drug can delay or halt the progression of disease is gathering steam.
- Esther Landhuis
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Article
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APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
A microglial state, featuring lipid droplets and secretion of neurotoxic factors, is shown to be most prominent in people with Alzheimer’s disease who have the APOE4 genotype.
- Michael S. Haney
- , Róbert Pálovics
- & Tony Wyss-Coray
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Article
| Open Access
A concerted neuron–astrocyte program declines in ageing and schizophrenia
A synaptic neuron and astrocyte program (SNAP) varies among healthy humans, may shape interindividual differences in synapses and plasticity, and is undermined in schizophrenia and with advancing age.
- Emi Ling
- , James Nemesh
- & Steven A. McCarroll
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Article
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Multisensory gamma stimulation promotes glymphatic clearance of amyloid
Audio and visual stimulation at 40 Hz promote cerebrospinal and interstitial fluid flux in mouse brain and result in amyloid clearance via the glymphatic system in a mouse model of Alzheimer’s disease.
- Mitchell H. Murdock
- , Cheng-Yi Yang
- & Li-Huei Tsai
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Article
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WNT signalling control by KDM5C during development affects cognition
The demethylase KDM5C, mutations in which often lead to intellectual disability, is identified as a crucial player in regulating the precise timing of neurodevelopment together with the WNT signalling pathway.
- Violetta Karwacki-Neisius
- , Ahram Jang
- & Yang Shi
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Article
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B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4
The immune system is tolerized against the neuromyelitis optica autoantigen AQP4 by thymic B cells, which present their endogenous AQP4 to AQP4-reactive thymocytes.
- Ali Maisam Afzali
- , Lucy Nirschl
- & Thomas Korn
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Article
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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 |
How CRISPR gene editing could help treat Alzheimer’s
Some researchers hoping that gene-editing technology can conquer forms of Alzheimer’s caused by genetic mutations.
- Tosin Thompson
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Article
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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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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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Article
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Sustained antidepressant effect of ketamine through NMDAR trapping in the LHb
The discrepancy between the short half-life of ketamine and its long-lasting effects is due to ketamine being trapped in NMDA receptors, and its release depends on neural activity in the lateral habenula.
- Shuangshuang Ma
- , Min Chen
- & Hailan Hu
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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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Article
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Assembloid CRISPR screens reveal impact of disease genes in human neurodevelopment
Assembloids are integrated with CRISPR screening to investigate the involvement of 425 neurodevelopmental disorder genes in human interneuron development, showing endoplasmic reticulum displacement before nuclear translocation and interference from LNPK deletion, resulting in abnormal migration.
- Xiangling Meng
- , David Yao
- & Sergiu P. Pașca
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Article
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Cingulate dynamics track depression recovery with deep brain stimulation
This study demonstrates how activity in the cingulate cortex tracks depression recovery, providing symptom relief using deep brain stimulation.
- Sankaraleengam Alagapan
- , Ki Sueng Choi
- & Christopher J. Rozell
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News |
Alzheimer’s drug trials plagued by lack of racial diversity
Under-representation of people of colour sparks concerns over the safety and efficacy of drugs in diverse populations.
- Sara Reardon
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Article
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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 |
Dementia risk linked to blood-protein imbalance in middle age
Abnormal levels of certain proteins — many of which have roles outside the brain — could be an early hallmark of Alzheimer’s disease or similar conditions.
- Lilly Tozer
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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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Article |
Co-transplantation of autologous Treg cells in a cell therapy for Parkinson’s disease
In mouse and rat models of Parkinson’s disease, co-transplanting regulatory T cells (Treg cells) improves the survival of grafted midbrain dopamine neurons in cell therapies by reducing the inflammatory response caused by surgical injury.
- Tae-Yoon Park
- , Jeha Jeon
- & Kwang-Soo Kim
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Article |
Remote neuronal activity drives glioma progression through SEMA4F
Callosal projection neurons located in the hemisphere contralateral to primary glioblastoma promote progression and widespread infiltration, and screening of axon guidance genes identified SEMA4F as a key regulator of tumourigenesis and activity-dependent progression.
- Emmet Huang-Hobbs
- , Yi-Ting Cheng
- & Benjamin Deneen
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Review Article |
The neuroscience of cancer
This Review examines the interplay between the nervous system and tumours, from cancer initiation to progression and metastasis.
- Rebecca Mancusi
- & Michelle Monje
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Matters Arising |
Ptbp1 deletion does not induce astrocyte-to-neuron conversion
- Thanh Hoang
- , Dong Won Kim
- & Seth Blackshaw
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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
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Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
Mouse models show that myelin dysfunction and associated inflammation increase with age, which can promote amyloid-β deposition and therefore risk of developing Alzheimer’s disease.
- Constanze Depp
- , Ting Sun
- & Klaus-Armin Nave
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Outlook |
Listening for neurological symptoms
Unusual vocal patterns can give clues that help to detect conditions such as Alzheimer’s disease.
- Michael Eisenstein
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News |
Alzheimer’s drug donanemab: what promising trial means for treatments
Results suggest that the amyloid-targeting drug candidate slows cognitive decline in some people, but questions remain over its potential side effects.
- Sara Reardon
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News Feature |
Conquering Alzheimer’s: a look at the therapies of the future
Researchers are looking to drug combinations, vaccines and gene therapy as they forge the next generation of treatments for the condition.
- Alison Abbott
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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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News |
Alzheimer’s drug saga prompts journal to scrutinize whistle-blowers
Publication requires complainants to disclose financial conflicts in the wake of controversy over Cassava Sciences’ experimental treatment simufilam.
- Holly Else
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News |
FDA approves Alzheimer’s drug lecanemab amid safety concerns
Reports of deaths potentially linked to the treatment have cast a shadow on what many hail as a landmark approval.
- Sara Reardon
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News & Views |
Swollen axons impair neuronal circuits in Alzheimer’s disease
Abnormal protein aggregates are a hallmark of Alzheimer’s disease. It emerges that these plaques cause swellings in neuronal projections called axons that prevent proper circuit function.
- Inma Cobos
- & Jorge J. Palop
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News |
Heralded Alzheimer’s drug works — but safety concerns loom
Eisai and Biogen share clinical trial data confirming that lecanemab slows mental decline, amid reports of potentially related deaths.
- McKenzie Prillaman
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Article
| Open Access
PLD3 affects axonal spheroids and network defects in Alzheimer’s disease
Amyloid-plaque-associated axonal spheroids are prominent contributors to neural network dysfunction in an Alzheimer’s model and can be reversed by endolysosomal modulation.
- Peng Yuan
- , Mengyang Zhang
- & Jaime Grutzendler
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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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News & Views |
Alzheimer’s risk variant APOE4 linked to myelin-assembly malfunction
People who carry a particular variant of the APOE gene are at increased risk of developing Alzheimer’s disease. It emerges that this might be due to decreased production of a fatty substance called myelin by oligodendrocyte cells.
- Karl Carlström
- & Gonçalo Castelo-Branco
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Nature Podcast |
How a key Alzheimer’s gene wreaks havoc in the brain
The mechanism of a gene implicated in Alzheimer’s disease, NASA’s Artemis rocket launch, and the latest news from COP27.
- Nick Petrić Howe
- & Benjamin Thompson
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News |
This is how an Alzheimer’s gene ravages the brain
Study in cells and mice suggests that the variant APOE4 affects the all-important insulation around nerve cells.
- Elie Dolgin
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Article |
APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes
APOE4 is associated with widespread gene expression changes across all cell types of the human brain, altered cholesterol homeostasis and transport signalling pathways, and decreased myelination in the brain.
- Joel W. Blanchard
- , Leyla Anne Akay
- & Li-Huei Tsai
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Article
| Open Access
Stroke genetics informs drug discovery and risk prediction across ancestries
A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.
- Aniket Mishra
- , Rainer Malik
- & Stephanie Debette
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News |
Alzheimer’s drug slows mental decline in trial — but is it a breakthrough?
Researchers are cautiously optimistic following companies’ announcement of positive results for lecanemab.
- McKenzie Prillaman
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Article |
Prenatal immune stress blunts microglia reactivity, impairing neurocircuitry
Aberrantly formed microglia due to an adverse prenatal environment affect long-term microglia reactivity and proper striatal circuit development in mice
- Lindsay N. Hayes
- , Kyongman An
- & Akira Sawa
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