ArticleScience translational medicine2020
A second X chromosome contributes to resilience in a mouse model of Alzheimer's disease.
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Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 3 of them syntheses that pooled it.
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124citing papers in PubMed, 3 pooled it
20.2field-weighted citation impact, top 1% of its field
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Who cites it
124 citing papers in PubMed, 3 syntheses or guidelines pooled it, 177 citations in OpenAlex.
- An umbrella review of candidate predictors of response, remission, recovery, and relapse across mental disorders.Molecular psychiatry · 2023Pooled it
- Distinct sex-specific DNA methylation differences in Alzheimer's disease.Alzheimer's research & therapy · 2022Pooled it
- Sex-specific DNA methylation differences in Alzheimer's disease pathology.Acta neuropathologica communications · 2021Pooled it
- Review
- Parent-of-origin effects in Alzheimer's liability dissociate neurocognitive and cardiovascular traits in at-risk individuals.Cell reports. Medicine · 2026Article
- A genome-wide investigation of depression among individuals with and without irritability.Molecular psychiatry · 2026Article
- Escape from X-chromosome inactivation: from gene discovery to regulatory mechanisms.Biochemical Society transactions · 2026Review
- Article
- Sex-linked helicases DDX3X and DDX3Y regulate G-quadruplex-associated stress in neurons.Cell death & disease · 2026Article
- Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Gonadal Sex and Sex-Chromosome Complement Interact to Affect Ethanol Consumption in Adolescent Four Core Genotypes Mice.Brain sciences · 2026Article
- Early, sex-dependent and progressive proteomic imbalance in the amygdala during Alzheimer´s disease continuum.Biology of sex differences · 2026Article
- Shared Risk Genes and Casual Relationships across Sex Hormone Related Traits and Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2026Article
- Sex Differences in Amyloid Pathology by Race, Ancestry, and Apolipoprotein E ε4 in an Admixed Autopsy Sample.JAMA neurology · 2026Article
- Sry-modified laboratory rat lines to study sex-chromosome effects underlying sex differences in physiology and disease: Four Core Genotypes and more.Biology of sex differences · 2026Article
- Estradiol modulates neuronal network hyperexcitability in select NDD risk genes.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial dysfunction in Alzheimer's disease and related sex differences.Frontiers in aging neuroscience · 2026Review
- Endurance training increases tmTNF-α and IL-6 levels in several vital organs in rats: relationship with hypoxia markers.Frontiers in molecular biosciences · 2026Article
- Epigenetic and transcriptomic alterations precede amyloidosis in the Alzheimer's disease AppScientific reports · 2025Article
- Xist in X chromosome inactivation: mechanisms and disease relevance.Cell communication and signaling : CCS · 2025Review
64 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 7 institutions in 1 country.
Emily J DavisDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-9878-1252
Lauren BroestlDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-6566-3986
Samira Abdulai-SaikuDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0003-3772-4646
Kurtresha WordenDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-5621-7979
Luke W BonhamDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-2533-1266
Elena Miñones-MoyanoDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-9007-8589
Arturo J MorenoDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0003-2357-5854
Dan WangDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Kevin ChangDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-6227-6430
Gina WilliamsDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Bayardo I GarayDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-1458-6095
Iryna LobachDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94158, USA.
Nino DevidzeGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Daniel KimGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Cliff Anderson-BergmanGladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.ORCID 0000-0002-4721-7472
Gui-Qiu YuGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Charles C WhiteBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.ORCID 0000-0001-9702-4516
Julie A HarrisAllen Institute for Brain Science, Seattle, WA 98109, USA.ORCID 0000-0003-0820-2021
Bruce L MillerDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-2152-4220
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA.ORCID 0000-0003-3689-554X
Arthur P ArnoldDepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-9908-9767
Phil L De JagerCenter for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.ORCID 0000-0002-8057-2505
Jorge J PalopDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-6086-1070
Barbara PanningDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Jennifer S YokoyamaDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Lennart MuckeDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0001-6256-9559
Dena B DubalDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA. dena.dubal@ucsf.edu.ORCID 0000-0001-7504-4372
University of California, San Francisco · USGladstone Institutes · USAllen Institute for Brain Science · USBroad Institute · USColumbia University Irving Medical Center · USRush University Medical Center · USUniversity of California, Los Angeles · US
Funding
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0MEngaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0MSUPPLEMENT 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
$43.3MPrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MILLER, BRUCE L · 2004 to 2018
$27.1MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MMulti-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7MPathway 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
$13.6MTransgenic Models to Study Alzheimer's DiseaseR37AG011385 · NIA · J. DAVID GLADSTONE INSTITUTES · PI MUCKE, LENNART · 2002 to 2011
$4.9MElucidating clinical heterogeneity in early-onset AD via genomics, transcriptomics, and neuroimagingR01AG062588 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOKOYAMA, JENNIFER S · 2019 to 2023
$4.0MBehavioral CoreP30NS065780 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI MUCKE, LENNART · 2011 to 2015
$4.0MOptogenetic dissection of cellular and circuit mechanisms of network dysfunction and amyloid deposition in mouse models of Alzheimer's disease in vivoRF1AG062234 · NIA · J. DAVID GLADSTONE INSTITUTES · PI PALOP, JORGE J · 2018 to 2021
$3.8MNCATS NIH HHS UL1 TR000004NIA NIH HHS K01 AG049152NIA NIH HHS K08 AG034531NIA NIH HHS P30 AG010161NIA NIH HHS P50 AG023501NIA NIH HHS R01 AG011385NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG062588NIA NIH HHS R01 AG062629NIA NIH HHS R37 AG011385NIA NIH HHS RF1 AG062234NIA NIH HHS RF1 AG068325NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NICHD NIH HHS R01 HD076125NIGMS NIH HHS R01 GM128431NINDS NIH HHS P30 NS065780NINDS NIH HHS R01 NS043196NINDS NIH HHS R01 NS092918
Abstract
A major sex difference in Alzheimer's disease (AD) is that men with the disease die earlier than do women. In aging and preclinical AD, men also show more cognitive deficits. Here, we show that the X chromosome affects AD-related vulnerability in mice expressing the human amyloid precursor protein (hAPP), a model of AD. XY-hAPP mice genetically modified to develop testicles or ovaries showed worse mortality and deficits than did XX-hAPP mice with either gonad, indicating a sex chromosome effect. To dissect whether the absence of a second X chromosome or the presence of a Y chromosome conferred a disadvantage on male mice, we varied sex chromosome dosage. With or without a Y chromosome, hAPP mice with one X chromosome showed worse mortality and deficits than did those with two X chromosomes. Thus, adding a second X chromosome conferred resilience to XY males and XO females. In addition, the Y chromosome, its sex-determining region Y gene (
Indexed as
Alzheimer DiseaseAnimalsFemaleMaleMiceSex CharacteristicsTestisX ChromosomeY Chromosome
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