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相关论文
53Alzheimer’s disease DNA methylation index (AD-DMI) and its association with late-life cognitive function
Nwanyieze Ngozi Jiakponnah•Ifechukwude J. Biose•Tracy Fischer•Katie Cherry•James Cronin等 7 人
Npj Dementia
2026
•2026/4/29
•Vol.2 No.1 p.330
Alzheimer’s disease (AD) is driven by genetic and epigenetic factors. A knowledge gap remains in applying DNA methylation (DNAm) to capture AD-specific signatures. We developed the AD DNA Methylation Index (AD-DMI), a brain-derived risk index constructed from 100 CpG sites identified by elastic-net ...
BiomarkersDiseasesGeneticsNeurologyNeuroscience
10.1038/S44400-026-00085-9
ISSN:3005-1940
SR-TWAS: leveraging multiple reference panels to improve transcriptome-wide association study power by ensemble machine learning
Randy L. Parrish•Aron S. Buchman•Shinya Tasaki•Yanling Wang•Denis Avey等 10 人
Nature Communications
2024
•2024/8/5
•Vol.15 No.1 p.1-16
Multiple reference panels of a given tissue or multiple tissues often exist, and multiple regression methods could be used for training gene expression imputation models for transcriptome-wide association studies (TWAS). To leverage expression imputation models (i.e., base models) trained with multi...
Alzheimer's diseaseGene expressionGenetic association studyParkinson's disease
10.1038/S41467-024-50983-W
ISSN:2041-1723
Abnormal brain cholesterol homeostasis in Alzheimer’s disease—a targeted metabolomic and transcriptomic study
Vijay R. Varma•H. Büşra Lüleci•Anup M. Oommen•Sudhir Varma•Chad T. Blackshear等 15 人
Npj Aging And Mechanisms Of Disease
2021
•2021/6/1
•Vol.7 No.1 p.1-14
The role of brain cholesterol metabolism in Alzheimer’s disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. W...
Alzheimer's disease
10.1038/S41514-021-00064-9
ISSN:2056-3973
Unbiased proteomics and multivariable regularized regression techniques identify SMOC1, NOG, APCS, and NTN1 in an Alzheimer’s disease brain proteomic signature
Jackson A. Roberts•Vijay R. Varma•Julián Candia•Toshiko Tanaka•Luigi Ferrucci等 7 人
Npj Aging
2023
•2023/7/6
•Vol.9 No.1 p.1-10
Advancements in omics methodologies have generated a wealth of high-dimensional Alzheimer’s disease (AD) datasets, creating significant opportunities and challenges for data interpretation. In this study, we utilized multivariable regularized regression techniques to identify a reduced set of protei...
Alzheimer's diseaseCognitive ageing
10.1038/S41514-023-00112-6
ISSN:2731-6068
A scalable approach to investigating sequence-to-function predictions from personal genomes
Anna E. Spiro•Xinming Tu•Yilun Sheng•Alexander Sasse•Rezwan Hosseini等 7 人
Nature Methods
2026
•2026/6/8
•00 p.1-5
Sequence-to-function (S2F) models can evaluate arbitrary DNA sequences, yet they struggle to fully capture inter-individual variation in gene expression. We introduce SAGE-net, a scalable framework for training and evaluating S2F models using personal genomes. While personal genome training improves...
Computational modelsGenomicsMachine learningSoftware
10.1038/S41592-026-03124-8
ISSN:1548-7091
A quantitative trait locus for reduced microglial APOE expression associates with reduced cerebral amyloid angiopathy
Michael E. Belloy•Jonathan Graff-Radford•Michael D. Greicius
Nature Genetics
2026
•2026/1/26
•Vol.58 No.2 p.271-272
Alzheimer's diseaseGene regulationGenetic association study
10.1038/S41588-025-02472-Z
ISSN:1061-4036
Single-nucleus multiregion transcriptomic analysis of brain vasculature in Alzheimer’s disease
Na Sun•Leyla Anne Akay•Mitchell H. Murdock•Yongjin Park•Fabiola Galiana-Melendez等 13 人
Nature Neuroscience
2023
•2023/6/1
•00 p.1-13
Cerebrovascular dysregulation is a hallmark of Alzheimer’s disease (AD), but the changes that occur in specific cell types have not been fully characterized. Here, we profile single-nucleus transcriptomes in the human cerebrovasculature in six brain regions from 220 individuals with AD and 208 age-m...
Alzheimer's diseaseBlood–brain barrierComputational biology and bioinformatics
10.1038/S41593-023-01334-3
ISSN:1097-6256
Brain microRNAs associated with late-life depressive symptoms are also associated with cognitive trajectory and dementia
Thomas S. Wingo•Jingjing Yang•Wen Fan•Se Min Canon•Ekaterina Sergeevna Gerasimov等 16 人
Npj Genomic Medicine
2020
•2020/2/6
•Vol.5 No.1 p.1-8
Late-life depression is associated with an increased risk for dementia but we have limited knowledge of the molecular mechanisms underlying this association. Here we investigated whether brain microRNAs, important posttranscriptional regulators of gene expression, contribute to this association. Lat...
DepressionMolecular medicine
10.1038/S41525-019-0113-8
ISSN:2056-7944
Multi-Omic analyses characterize the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer’s disease
Baloni Priyanka•Arnold Matthias•Buitrago Luna•Nho Kwangsik•Moreno Herman等 22 人
Communications Biology
2022
•2022/10/8
•Vol.5 No.1 p.1-13
Dysregulation of sphingomyelin and ceramide metabolism have been implicated in Alzheimer’s disease. Genome-wide and transcriptome-wide association studies have identified various genes and genetic variants in lipid metabolism that are associated with Alzheimer’s disease. However, the molecular mecha...
Alzheimer's diseaseNeuroscience
10.1038/S42003-022-04011-6
ISSN:2399-3642
Social activity mediates locus coeruleus tangle-related cognition in older adults
Benjamin S. Zide•Nancy J. Donovan•Soyoung Lee•Sukriti Nag•David A. Bennett等 6 人
Molecular Psychiatry
2024
•2024/2/15
•00 p.1-8
The locus coeruleus-noradrenaline system regulates brain-wide neural activity involved in cognition and behavior. Integrity of this subcortical neuromodulatory system is proposed to be a substrate of cognitive reserve that may be strengthened by lifetime cognitive and social activity. Conversely, ac...
DiseasesPredictive markers
10.1038/S41380-024-02467-Y
ISSN:1359-4184
CHRNA5 links chandelier cells to severity of amyloid pathology in aging and Alzheimer’s disease
Jonas Rybnicek•Yuxiao Chen•Milos Milic•Earvin S. Tio•JoAnne McLaurin等 13 人
Translational Psychiatry
2024
•2024/2/8
•Vol.14 No.1 p.1-13
Changes in high-affinity nicotinic acetylcholine receptors are intricately connected to neuropathology in Alzheimer’s Disease (AD). Protective and cognitive-enhancing roles for the nicotinic α5 subunit have been identified, but this gene has not been closely examined in the context of human aging an...
Clinical geneticsMolecular neuroscience
10.1038/S41398-024-02785-3
ISSN:2158-3188
Inferring protein expression changes from mRNA in Alzheimer’s dementia using deep neural networks
Tasaki Shinya•Xu Jishu•Avey Denis R.•Johnson Lynnaun•Petyuk Vladislav A.等 9 人
Nature Communications
2022
•2022/2/3
•Vol.13 No.1 p.1-15
Identifying the molecular systems and proteins that modify the progression of Alzheimer’s disease and related dementias (ADRD) is central to drug target selection. However, discordance between mRNA and protein abundance, and the scarcity of proteomic data, has limited our ability to advance candidat...
Alzheimer's diseaseSystems biology
10.1038/S41467-022-28280-1
ISSN:2041-1723
Stroke genetics informs drug discovery and risk prediction across ancestries
Mishra Aniket•Malik Rainer•Hachiya Tsuyoshi•Jürgenson Tuuli•Namba Shinichi等 187 人
Nature
2022
•2022/9/30
•Vol.611 No.7934 p.115-123
Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 3...
Genetic markersGenome-wide association studiesPredictive markersStroke
10.1038/S41586-022-05165-3
ISSN:0028-0836
Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation
Erik C. B. Johnson•Eric B. Dammer•Duc M. Duong•Lingyan Ping•Maotian Zhou等 33 人
Nature Medicine
2020
•2020/4/13
•Vol.26 No.5 p.769-780
Our understanding of Alzheimer’s disease (AD) pathophysiology remains incomplete. Here we used quantitative mass spectrometry and coexpression network analysis to conduct the largest proteomic study thus far on AD. A protein network module linked to sugar metabolism emerged as one of the modules mos...
Alzheimer's diseaseDiagnostic markersProteome informaticsSystems analysis
10.1038/S41591-020-0815-6
ISSN:1078-8956
Dissecting the human leptomeninges at single-cell resolution
Nicola A. Kearns•Artemis Iatrou•Daniel J. Flood•Sashini De Tissera•Zachary M. Mullaney等 9 人
Nature Communications
2023
•2023/11/3
•Vol.14 No.1 p.1-16
Emerging evidence shows that the meninges conduct essential immune surveillance and immune defense at the brain border, and the dysfunction of meningeal immunity contributes to aging and neurodegeneration. However, no study exists on the molecular properties of cell types within human leptomeninges....
Functional clusteringMolecular neuroscienceNeurodegenerationTranscriptomics
10.1038/S41467-023-42825-Y
ISSN:2041-1723
Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition
Elisenda Bueichekú•Ibai Diez•Chan-Mi Kim•John Alex Becker•Elouise A. Koops等 14 人
Nature Aging
2024
•2024/4/25
•00 p.1-13
Autopsy studies indicated that the locus coeruleus (LC) accumulates hyperphosphorylated tau before allocortical regions in Alzheimer’s disease. By combining in vivo longitudinal magnetic resonance imaging measures of LC integrity, tau positron emission tomography imaging and cognition with autopsy d...
AgeingNeurosciencePredictive markers
10.1038/S43587-024-00626-Y
ISSN:2662-8465
Predictive network analysis identifies JMJD6 and other potential key drivers in Alzheimer’s disease
Julie P. Merchant•Kuixi Zhu•Marc Y. R. Henrion•Syed S. A. Zaidi•Branden Lau等 12 人
Communications Biology
2023
•2023/5/15
•Vol.6 No.1 p.1-19
Despite decades of genetic studies on late-onset Alzheimer’s disease, the underlying molecular mechanisms remain unclear. To better comprehend its complex etiology, we use an integrative approach to build robust predictive (causal) network models using two large human multi-omics datasets. We deline...
Alzheimer's diseaseBayesian inference
10.1038/S42003-023-04791-5
ISSN:2399-3642
Interpretable deep learning framework for understanding molecular changes in human brains with Alzheimer’s disease: implications for microglia activation and sex differences
Maitry Ronakbhai Trivedi•Amogh Manoj Joshi•Jay Shah•Benjamin P. Readhead•Melissa A. Wilson等 9 人
Npj Aging
2025
•2025/7/16
•Vol.11 No.1 p.1-15
The utilization of artificial intelligence in studying the dysregulation of gene expression in Alzheimer’s disease (AD) affected brain tissues remains underexplored, particularly in delineating common and specific transcriptomic signatures across different brain regions implicated in AD-related cell...
Alzheimer's disease
10.1038/S41514-025-00258-5
ISSN:2731-6068
Reply to: a quantitative trait locus for reduced microglial APOE expression associates with reduced cerebral amyloid angiopathy
Lincoln M. P. Shade•Qi Qiao•Yuriko Katsumata•Shubhabrata Mukherjee•Jai G. Broome等 9 人
Nature Genetics
2026
•2026/1/26
•Vol.58 No.2 p.273-274
Alzheimer's diseaseGenetics research
10.1038/S41588-025-02473-Y
ISSN:1061-4036
Cell-type-specific Alzheimer’s disease polygenic risk scores are associated with distinct disease processes in Alzheimer’s disease
Hyun-Sik Yang•Ling Teng•Daniel Kang•Vilas Menon•Tian Ge等 17 人
Nature Communications
2023
•2023/11/30
•Vol.14 No.1 p.1-13
Many of the Alzheimer’s disease (AD) risk genes are specifically expressed in microglia and astrocytes, but how and when the genetic risk localizing to these cell types contributes to AD pathophysiology remains unclear. Here, we derive cell-type-specific AD polygenic risk scores (ADPRS) from two ext...
Alzheimer's diseaseAstrocyteMicrogliaPersonalized medicine
10.1038/S41467-023-43132-2
ISSN:2041-1723
A neurodegeneration checkpoint mediated by REST protects against the onset of Alzheimer’s disease
Liviu Aron•Chenxi Qiu•Zhen Kai Ngian•Marianna Liang•Derek Drake等 16 人
Nature Communications
2023
•2023/11/2
•Vol.14 No.1 p.1-22
Many aging individuals accumulate the pathology of Alzheimer’s disease (AD) without evidence of cognitive decline. Here we describe an integrated neurodegeneration checkpoint response to early pathological changes that restricts further disease progression and preserves cognitive function. Checkpoin...
Alzheimer's diseaseNeural ageing
10.1038/S41467-023-42704-6
ISSN:2041-1723
Identifying individuals with high risk of Alzheimer’s disease using polygenic risk scores
Ganna Leonenko•Emily Baker•Joshua Stevenson-Hoare•Annerieke Sierksma•Mark Fiers等 8 人
Nature Communications
2021
•2021/7/23
•Vol.12 No.1 p.1-10
Polygenic Risk Scores (PRS) for AD offer unique possibilities for reliable identification of individuals at high and low risk of AD. However, there is little agreement in the field as to what approach should be used for genetic risk score calculations, how to model the effect of APOE, what the optim...
Alzheimer's diseaseGeneticsGenome-wide association studiesNeurology
10.1038/S41467-021-24082-Z
ISSN:2041-1723
Multicellular communities are perturbed in the aging human brain and Alzheimer’s disease
Anael Cain•Mariko Taga•Cristin McCabe•Gilad S. Green•Idan Hekselman等 17 人
Nature Neuroscience
2023
•2023/6/19
•00 p.1-14
The role of different cell types and their interactions in Alzheimer’s disease (AD) is a complex and open question. Here, we pursued this question by assembling a high-resolution cellular map of the aging frontal cortex using single-nucleus RNA sequencing of 24 individuals with a range of clinicopat...
Alzheimer's diseaseData processingGene expression profilingMolecular neuroscience
10.1038/S41593-023-01356-X
ISSN:1097-6256
INPP5D regulates inflammasome activation in human microglia
Vicky Chou•Richard V. Pearse•Aimee J. Aylward•Nancy Ashour•Mariko Taga等 17 人
Nature Communications
2023
•2023/11/29
•Vol.14 No.1 p.1-23
Microglia and neuroinflammation play an important role in the development and progression of Alzheimer’s disease (AD). Inositol polyphosphate-5-phosphatase D (INPP5D/SHIP1) is a myeloid-expressed gene genetically-associated with AD. Through unbiased analyses of RNA and protein profiles in INPP5D-dis...
Alzheimer's diseaseCellular neuroscienceMicrogliaNeuroimmunology
10.1038/S41467-023-42819-W
ISSN:2041-1723
Integrative transcriptome analyses of the aging brain implicate altered splicing in Alzheimer’s disease susceptibility
Towfique Raj•Yang I. Li•Garrett Wong•Jack Humphrey•Minghui Wang等 17 人
Nature Genetics
2018
•2018/10/8
•Vol.50 No.11 p.1584-1592
Here we use deep sequencing to identify sources of variation in mRNA splicing in the dorsolateral prefrontal cortex (DLPFC) of 450 subjects from two aging cohorts. Hundreds of aberrant pre-mRNA splicing events are reproducibly associated with Alzheimer’s disease. We also generate a catalog of splici...
Gene expression profilingNeurological disordersTranscriptomics
10.1038/S41588-018-0238-1
ISSN:1061-4036
Single-cell multiregion dissection of Alzheimer’s disease
Hansruedi Mathys•Carles A. Boix•Leyla Anne Akay•Ziting Xia•Jose Davila-Velderrain等 20 人
Nature
2024
•2024/7/24
•00 p.1-11
Alzheimer’s disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood1–3. Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1....
Alzheimer's diseaseGene expressionMolecular neuroscience
10.1038/S41586-024-07606-7
ISSN:0028-0836
Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease
Yingyue Zhou•Wilbur M. Song•Prabhakar S. Andhey•Amanda Swain•Tyler Levy等 25 人
Nature Medicine
2020
•2020/1/13
•Vol.26 No.1 p.131-142
Glia have been implicated in Alzheimer’s disease (AD) pathogenesis. Variants of the microglia receptor triggering receptor expressed on myeloid cells 2 (TREM2) increase AD risk, and activation of disease-associated microglia (DAM) is dependent on TREM2 in mouse models of AD. We surveyed gene-express...
Alzheimer's diseaseNeuroimmunology
10.1038/S41591-019-0695-9
ISSN:1078-8956
Ultra-high field imaging, plasma markers and autopsy data uncover a specific rostral locus coeruleus vulnerability to hyperphosphorylated tau
Van Egroo Maxime•Riphagen Joost M.•Ashton Nicholas J.•Janelidze Shorena•Sperling Reisa A.等 12 人
Molecular Psychiatry
2023
•2023/4/5
•00 p.1-11
Autopsy data indicate that the locus coeruleus (LC) is one of the first sites in the brain to accumulate hyperphosphorylated tau pathology, with the rostral part possibly being more vulnerable in the earlier stages of the disease. Taking advantage of recent developments in ultra-high field (7 T) ima...
BiomarkersNeuroscience
10.1038/S41380-023-02041-Y
ISSN:1359-4184
Cell-type-aware transcriptome-wide association studies identify 91 independent risk genes for Alzheimer’s disease dementia
Qiang Liu•Randy L. Parrish•Shizhen Tang•Shinya Tasaki•David A. Bennett等 10 人
Communications Biology
2026
•2026/4/22
0Most existing transcriptome wide association studies (TWASs) of Alzheimer’s Disease (AD) dementia only use bulk RNA-seq data and a single statistical method. Here, we utilize an omnibus TWAS (TWAS-O) pipeline that leverages multiple complementary statistical methods to integrate the snRNA-seq datase...
Alzheimer's diseaseGene expressionGenetic association study
10.1038/S42003-026-10030-4
ISSN:2399-3642
Integrating whole-genome sequencing with multi-omic data reveals the impact of structural variants on gene regulation in the human brain
Vialle Ricardo A.•de Paiva Lopes Katia•Bennett David A.•Crary John F.•Raj Towfique
Nature Neuroscience
2022
•2022/3/14
•00 p.1-11
Structural variants (SVs), which are genomic rearrangements of more than 50 base pairs, are an important source of genetic diversity and have been linked to many diseases. However, it remains unclear how they modulate human brain function and disease risk. Here we report 170,996 SVs discovered using...
Functional genomicsGene regulationGenetic association studyNeurodegeneration
10.1038/S41593-022-01031-7
ISSN:1097-6256
Continuous assessment of daily-living gait using self-supervised learning of wrist-worn accelerometer data
Yonatan E. Brand•Aron S. Buchman•Felix Kluge•Luca Palmerini•Clemens Becker等 14 人
Npj Digital Medicine
2026
•2026/3/12
0Physical activity and mobility are critical for healthy aging and predict diverse health outcomes. While wrist-worn accelerometers are widely used to monitor physical activity, estimating gait metrics from wrist data remains challenging. We extend ElderNet, a self-supervised deep-learning model prev...
BiomarkersBiomedical engineering
10.1038/S41746-026-02528-2
ISSN:2398-6352
Explainable deep learning approach for extracting cognitive features from hand-drawn images of intersecting pentagons
Shinya Tasaki•Namhee Kim•Tim Truty•Ada Zhang•Aron S. Buchman等 7 人
Npj Digital Medicine
2023
•2023/8/23
•Vol.6 No.1 p.1-12
Hand drawing, which requires multiple neural systems for planning and controlling sequential movements, is a useful cognitive test for older adults. However, the conventional visual assessment of these drawings only captures limited attributes and overlooks subtle details that could help track cogni...
BiomarkersNeurological disorders
10.1038/S41746-023-00904-W
ISSN:2398-6352
Integrative brain omics approach highlights sn-1 lysophosphatidylethanolamine in Alzheimer’s dementia
Chih-Yu Chen•Kristal Maner-Smith•Manoj Khadka•Jun Ahn•Xueyun L. Gulbin等 11 人
Nature Communications
2025
•2025/10/31
•Vol.16 No.1 p.1-17
The biology of individual lipid species and their relevance in Alzheimer’s disease (AD) remains incompletely understood. To explore the lipidomic biomarkers associated with cognition function and neuropathological changes in AD, we utilize non-targeted mass spectrometry on 316 post-mortem brains fro...
Alzheimer's diseaseLipidomics
10.1038/S41467-025-64328-8
ISSN:2041-1723
A cerebrospinal fluid synaptic protein biomarker for prediction of cognitive resilience versus decline in Alzheimer’s disease
Hamilton Se-Hwee Oh•Deniz Yagmur Urey•Linda Karlsson•Zeyu Zhu•Yuanyuan Shen等 38 人
Nature Medicine
2025
•2025/3/31
•00 p.1-12
Rates of cognitive decline in Alzheimer’s disease (AD) are extremely heterogeneous. Although biomarkers for amyloid-beta (Aβ) and tau proteins, the hallmark AD pathologies, have improved pathology-based diagnosis, they explain only 20–40% of the variance in AD-related cognitive impairment (CI). To d...
Alzheimer's diseaseCognitive ageingPrognostic markersProteome informatics
10.1038/S41591-025-03565-2
ISSN:1078-8956
Sex and APOE ε4 genotype modify the Alzheimer’s disease serum metabolome
Matthias Arnold•Kwangsik Nho•Alexandra Kueider-Paisley•Tyler Massaro•Kevin Huynh等 30 人
Nature Communications
2020
•2020/3/2
•Vol.11 No.1 p.1-12
Late-onset Alzheimer’s disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD that also give rise to large metabolic differences. We systematically investigated group-specific metabolic alterations by conducting...
Alzheimer's diseaseMetabolomicsPredictive markers
10.1038/S41467-020-14959-W
ISSN:2041-1723
White matter micro- and macrostructure brain charts for the human lifespan
Michael E. Kim•Chenyu Gao•Karthik Ramadass•Nancy R. Newlin•Praitayini Kanakaraj等 30 人
Nature
2026
•2026/5/13
•00 p.1-11
The human brain relies on a complex network of connections to function, with white matter acting as the primary communication highway between different brain regions1,2. Disruptions in these critical communication pathways are linked to several neurological, psychiatric and developmental disorders3,...
Brain imagingData processing
10.1038/S41586-026-10454-2
ISSN:0028-0836
AutoFocus: a hierarchical framework to explore multi-omic disease associations spanning multiple scales of biomolecular interaction
Annalise Schweickart•Kelsey Chetnik•Richa Batra•Rima Kaddurah-Daouk•Karsten Suhre等 7 人
Communications Biology
2024
•2024/9/6
•Vol.7 No.1 p.1-14
Recent advances in high-throughput measurement technologies have enabled the analysis of molecular perturbations associated with disease phenotypes at the multi-omic level. Such perturbations can range in scale from fluctuations of individual molecules to entire biological pathways. Data-driven clus...
Data integrationFunctional clustering
10.1038/S42003-024-06724-2
ISSN:2399-3642
Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions
Selina M. Vattathil•Ekaterina S. Gerasimov•Se Min Canon•Adriana Lori•Sarah Sze Min Tan等 11 人
Nature Aging
2024
•2024/12/6
•00 p.1-14
MicroRNAs (miRNAs) play a crucial role in regulating gene expression and influence many biological processes. Despite their importance, understanding of how genetic variation affects miRNA expression in the brain and how this relates to brain disorders remains limited. Here we investigated these que...
AgeingBrainGene expressionGene regulation
10.1038/S43587-024-00778-X
ISSN:2662-8465
Interplay between age, APOE Ɛ4 and the metabolome in plasma and brain in Alzheimer’s disease
Najaf Amin•Jun Liu•William Sproviero•Matthias Arnold•Richa Batra等 20 人
Translational Psychiatry
2025
•2025/10/31
•Vol.15 No.1 p.1-15
Age and the ε4 variant of the apolipoprotein E gene (APOE ε4) are two major drivers of Alzheimer’s disease (AD). APOE is also the major determinant of longevity. How age and APOE interact in the development of AD is largely unknown. In this study we integrate metabolomics (N = 274,259) and proteomic...
DiseasesMolecular neuroscience
10.1038/S41398-025-03625-8
ISSN:2158-3188
Cellular communities reveal trajectories of brain ageing and Alzheimer’s disease
Gilad Sahar Green•Masashi Fujita•Hyun-Sik Yang•Mariko Taga•Anael Cain等 18 人
Nature
2024
•2024/8/28
•00 p.1-12
Alzheimer’s disease (AD) has recently been associated with diverse cell states1–11, yet when and how these states affect the onset of AD remains unclear. Here we used a data-driven approach to reconstruct the dynamics of the brain’s cellular environment and identified a trajectory leading to AD that...
Alzheimer's diseaseGene expressionGlial biology
10.1038/S41586-024-07871-6
ISSN:0028-0836
Integration across biophysical scales identifies molecular and cellular correlates of person-to-person variability in human brain connectivity
Bernard Ng•Shinya Tasaki•Kelsey M. Greathouse•Courtney K. Walker•Ada Zhang等 20 人
Nature Neuroscience
2024
•2024/10/31
•Vol.27 No.11 p.2240-2252
Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected a...
Cellular neuroscienceFunctional magnetic resonance imagingGenetics of the nervous systemNetwork models
10.1038/S41593-024-01788-Z
ISSN:1097-6256
Benchmarking of deep neural networks for predicting personal gene expression from DNA sequence highlights shortcomings
Alexander Sasse•Bernard Ng•Anna E. Spiro•Shinya Tasaki•David A. Bennett等 9 人
Nature Genetics
2023
•2023/11/30
•00 p.1-5
Deep learning methods have recently become the state of the art in a variety of regulatory genomic tasks1–6, including the prediction of gene expression from genomic DNA. As such, these methods promise to serve as important tools in interpreting the full spectrum of genetic variation observed in per...
Data miningGene expression profilingSequence annotation
10.1038/S41588-023-01524-6
ISSN:1061-4036
Lithium deficiency and the onset of Alzheimer’s disease
Liviu Aron•Zhen Kai Ngian•Chenxi Qiu•Jaejoon Choi•Marianna Liang等 14 人
Nature
2025
•2025/8/6
•00 p.1-10
The earliest molecular changes in Alzheimer’s disease (AD) are poorly understood1–5. Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced ...
Alzheimer's diseaseMolecular neuroscience
10.1038/S41586-025-09335-X
ISSN:0028-0836
Large-scale deep multi-layer analysis of Alzheimer’s disease brain reveals strong proteomic disease-related changes not observed at the RNA level
Johnson Erik C. B.•Carter E. Kathleen•Dammer Eric B.•Duong Duc M.•Gerasimov Ekaterina S.等 24 人
Nature Neuroscience
2022
•2022/2/3
•Vol.25 No.2 p.213-225
The biological processes that are disrupted in the Alzheimer’s disease (AD) brain remain incompletely understood. In this study, we analyzed the proteomes of more than 1,000 brain tissues to reveal new AD-related protein co-expression modules that were highly preserved across cohorts and brain regio...
Alzheimer's diseaseBiochemical networksMass spectrometryProteomic analysis
10.1038/S41593-021-00999-Y
ISSN:1097-6256
GWAS of multiple neuropathology endophenotypes identifies new risk loci and provides insights into the genetic risk of dementia
Lincoln M. P. Shade•Yuriko Katsumata•Erin L. Abner•Khine Zin Aung•Steven A. Claas等 23 人
Nature Genetics
2024
•2024/10/8
•00 p.1-15
Genome-wide association studies (GWAS) have identified >80 Alzheimer’s disease and related dementias (ADRD)-associated genetic loci. However, the clinical outcomes used in most previous studies belie the complex nature of underlying neuropathologies. Here we performed GWAS on 11 ADRD-related neur...
Alzheimer's diseaseCerebrovascular disordersGenome-wide association studies
10.1038/S41588-024-01939-9
ISSN:1061-4036
Shared proteomic effects of cerebral atherosclerosis and Alzheimer’s disease on the human brain
Aliza P. Wingo•Wen Fan•Duc M. Duong•Ekaterina S. Gerasimov•Eric B. Dammer等 18 人
Nature Neuroscience
2020
•2020/5/18
•Vol.23 No.6 p.696-700
Cerebral atherosclerosis contributes to dementia via unclear processes. We performed proteomic sequencing of dorsolateral prefrontal cortex in 438 older individuals and found associations between cerebral atherosclerosis and reduced synaptic signaling and RNA splicing and increased oligodendrocyte d...
Alzheimer's diseaseCerebrovascular disordersProteomic analysis
10.1038/S41593-020-0635-5
ISSN:1097-6256
Regulation of lifespan by neural excitation and REST
Joseph M. Zullo•Derek Drake•Liviu Aron•Patrick O’Hern•Sameer C. Dhamne等 13 人
Nature
2019
•2019/10/16
•Vol.574 No.7778 p.359-364
The mechanisms that extend lifespan in humans are poorly understood. Here we show that extended longevity in humans is associated with a distinct transcriptome signature in the cerebral cortex that is characterized by downregulation of genes related to neural excitation and synaptic function. In Cae...
Gene regulationNeural ageing
10.1038/S41586-019-1647-8
ISSN:0028-0836
Epigenome-wide study uncovers large-scale changes in histone acetylation driven by tau pathology in aging and Alzheimer’s human brains
Hans-Ulrich Klein•Cristin McCabe•Elizabeta Gjoneska•Sarah E. Sullivan•Belinda J. Kaskow等 17 人
Nature Neuroscience
2018
•2018/12/17
•Vol.22 No.1 p.37-46
Accumulation of tau and amyloid-β are two pathologic hallmarks of Alzheimer’s disease. We conducted an epigenome-wide association study using the histone 3 lysine 9 acetylation (H3K9ac) mark in 669 aged human prefrontal cortices; in contrast with amyloid-β, tau protein burden had a broad effect on t...
Alzheimer's diseaseChromatin remodellingDementiaEpigenetics in the nervous systemHistone post-translational modifications
10.1038/S41593-018-0291-1
ISSN:1097-6256
G-protein coupled estrogen receptor 1, amyloid-β, and tau tangles in older adults
Shahram Oveisgharan•Lei Yu•Katia de Paiva Lopes•Vladislav A. Petyuk•Shinya Tasaki等 11 人
Communications Biology
2024
•2024/5/15
•Vol.7 No.1 p.1-9
Accumulation of amyloid-β (Aβ) and tau tangles are hallmarks of Alzheimer’s disease. Aβ is extracellular while tau tangles are typically intracellular, and it is unknown how these two proteinopathies are connected. Here, we use data of 1206 elders and test that RNA expression levels of GPER1, a tran...
Alzheimer's diseaseMolecular neuroscience
10.1038/S42003-024-06272-9
ISSN:2399-3642
Systems genetic dissection of brain gene expression reveals excitotoxic mechanisms of Alzheimer’s disease
Pinghan Zhao•Omar El Fadel•Anh Le•Carl Grant Mangleburg•Justin Dhindsa等 17 人
Molecular Psychiatry
2026
•2026/2/14
•00 p.1-20
Gene expression changes likely mediate the impact of Alzheimer’s disease (AD) neuropathology on cognition, but there are challenges to resolve the proximal causal pathways from postmortem brain transcriptome profiles which lack temporal resolution and are further confounded by mixed pathologies. Her...
GeneticsNeurosciencePsychiatric disorders
10.1038/S41380-026-03479-6
ISSN:1359-4184
Individual bioenergetic capacity as a potential source of resilience to Alzheimer’s disease
Matthias Arnold•Mustafa Buyukozkan•P. Murali Doraiswamy•Kwangsik Nho•Tong Wu等 18 人
Nature Communications
2025
•2025/2/24
•Vol.16 No.1 p.1-15
Impaired glucose uptake in the brain is an early presymptomatic manifestation of Alzheimer’s disease (AD), with symptom-free periods of varying duration that likely reflect individual differences in metabolic resilience. We propose a systemic “bioenergetic capacity”, the individual ability to mainta...
Alzheimer's diseaseMetabolomics
10.1038/S41467-025-57032-0
ISSN:2041-1723
Large-scale plasma proteomic profiling unveils diagnostic biomarkers and pathways for Alzheimer’s disease
Gyujin Heo•Ying Xu•Erming Wang•Muhammad Ali•Hamilton Se-Hwee Oh等 38 人
Nature Aging
2025
•2025/5/20
•00 p.1-18
Proteomic studies have been instrumental in identifying brain, cerebrospinal fluid and plasma proteins associated with Alzheimer’s disease (AD). Here, we comprehensively examined 6,905 aptamers corresponding to 6,106 unique proteins in plasma in more than 3,300 well-characterized individuals to iden...
Alzheimer's diseaseDiagnostic markers
10.1038/S43587-025-00872-8
ISSN:2662-8465
3D bioengineered neural tissue generated from patient-derived iPSCs mimics time-dependent phenotypes and transcriptional features of Alzheimer’s disease
Selene Lomoio•Ravi S. Pandey•Nicolas Rouleau•Beatrice Menicacci•WonHee Kim等 12 人
Molecular Psychiatry
2023
•2023/6/26
•00 p.1-12
Several iPSC-derived three-dimensional (3D) cultures have been generated to model Alzheimer’s disease (AD). While some AD-related phenotypes have been identified across these cultures, none of them could recapitulate multiple AD-related hallmarks in one model. To date, the transcriptomic features of...
Cell biologyNeuroscience
10.1038/S41380-023-02147-3
ISSN:1359-4184