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Fröhlich, A.S.* ; Gerstner, N. ; Gagliardi, M.* ; Ködel, M.* ; Yusupov, N.* ; Matosin, N.* ; Czamara, D.* ; Sauer, S.* ; Roeh, S.* ; Murek, V.* ; Chatzinakos, C.* ; Daskalakis, N.P.* ; Knauer-Arloth, J. ; Ziller, M.J.* ; Binder, E.B.*

Single-nucleus transcriptomic profiling of human orbitofrontal cortex reveals convergent effects of aging and psychiatric disease.

Nat. Neurosci. 27, 2021-2032 (2024)
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Aging is a complex biological process and represents the largest risk factor for neurodegenerative disorders. The risk for neurodegenerative disorders is also increased in individuals with psychiatric disorders. Here, we characterized age-related transcriptomic changes in the brain by profiling ~800,000 nuclei from the orbitofrontal cortex from 87 individuals with and without psychiatric diagnoses and replicated findings in an independent cohort with 32 individuals. Aging affects all cell types, with LAMP5+LHX6+ interneurons, a cell-type abundant in primates, by far the most affected. Disrupted synaptic transmission emerged as a convergently affected pathway in aged tissue. Age-related transcriptomic changes overlapped with changes observed in Alzheimer's disease across multiple cell types. We find evidence for accelerated transcriptomic aging in individuals with psychiatric disorders and demonstrate a converging signature of aging and psychopathology across multiple cell types. Our findings shed light on cell-type-specific effects and biological pathways underlying age-related changes and their convergence with effects driven by psychiatric diagnosis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gene-expression; Quantile Normalization; Bioconductor Package; Alzheimers-disease; Brain; Age; Neurodegeneration; Association; Microglia; Lingo-1
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 1097-6256
e-ISSN 1546-1726
Journal Nature Neuroscience
Quellenangaben Volume: 27, Issue: 10, Pages: 2021-2032 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503800-001
Grants National Institute of Alcohol Abuse and Alcoholism of the National Institutes of Health
Hope for Depression Research Foundation
BMBF eMED program grant DINGS
Alexander von Humboldt Foundation
Joachim Herz Foundation - Else-Kroener-Fresenius Foundation
Brain & Behavior Research Foundation
National Institute of Mental Health
New South Wales Brain Tissue Resource Centre at the University of Sydney
University of Sydney
Nathalie Gerstner is supported by the Joachim Herz Foundation.
DOI 10.1038/s41593-024-01742-z
WOS ID 001304673100001
Scopus ID 85203165419
PubMed ID 39227716
Erfassungsdatum 2024-10-14
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