ArticlebioRxiv : the preprint server for biology2026
Neuroticism is linked to cognitive decline and increased risk of Alzheimer's disease through dysregulation of excitatory neurons.
Sneha Sharma, Natacha Comandante-Lou, Yiyi Ma, Masashi Fujita, David A Bennett, Andrea R Zammit, Philip L De Jager
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In one paragraphArticle in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
7 authors.
Sneha SharmaCenter for Translational and Computational Neuroimmunology, Columbia University Irving Medical Center, Department of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, New York, NY, 10032, United States of America.ORCID 0009-0006-5401-9796 Natacha Comandante-LouCenter for Translational and Computational Neuroimmunology, Columbia University Irving Medical Center, Department of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, New York, NY, 10032, United States of America.ORCID 0000-0002-7981-7333 Yiyi MaCenter for Translational and Computational Neuroimmunology, Columbia University Irving Medical Center, Department of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, New York, NY, 10032, United States of America.
Masashi FujitaCenter for Translational and Computational Neuroimmunology, Columbia University Irving Medical Center, Department of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, New York, NY, 10032, United States of America.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, United States of America.
Andrea R ZammitRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, 60612, United States of America.
Philip L De JagerCenter for Translational and Computational Neuroimmunology, Columbia University Irving Medical Center, Department of Neurology and the Taub Institute for the Study of Alzheimer's Disease and the Aging Brain, New York, NY, 10032, United States of America.
Funding
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MRush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MPathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6MAlzheimer variants: Propagation of shared functional changes across cellular networksU01AG072572 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DE JAGER, PHILIP L, ST GEORGE-HYSLOP, PETER HENRY · 2021 to 2025
$8.5MNIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG072572
6 · The paper itselfAbstract
Introduction: Neuroticism is an established risk factor for Alzheimer's disease (AD), yet the molecular mechanisms linking this personality trait to neurodegeneration remain poorly understood. Methods: We leveraged single-nucleus RNA-sequencing data from longitudinal cohort studies of cognitive aging (n = 655) to investigate the mechanisms mediating the association between neuroticism and AD. Results: We identified two genes associated with neuroticism, both of which are downregulated in excitatory neurons: Discussion: The dysregulation of excitatory neurons may represent a key cellular change that links neuroticism to AD.
Indexed as
Alzheimer’s diseasecognitive declineexcitatory neuronsneuroticism
Identifiers
PMID42427719
PMCPMC13345058
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