ArticleNeurology2022
Association of AK4 Protein From Stem Cell-Derived Neurons With Cognitive Reserve: An Autopsy Study.
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Article in Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
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Who cites it
12 citing papers in PubMed, 10 citations in OpenAlex.
- Neuropathologic Profiles and Associated Cognitive Trajectories in Community-Living Older Adults.JAMA network open · 2026Article
- MAPK3 as a ferroptosis driver in excitatory neurons in Alzheimer's disease: from genetic causal inference toFrontiers in aging neuroscience · 2026Article
- Gene module-trait network analysis uncovers cell type specific systems and genes relevant to Alzheimer's Disease.Acta neuropathologica communications · 2025Article
- Molecular hallmarks of excitatory and inhibitory neuronal resilience to Alzheimer's disease.Molecular neurodegeneration · 2025Article
- The temporal onset of associations of cortical proteins with cognitive resilience vary during late life.Neurobiology of disease · 2025Article
- Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025Review
- Translating the Post-Mortem Brain Multi-Omics Molecular Taxonomy of Alzheimer's Dementia to Living Humans.bioRxiv : the preprint server for biology · 2025Article
- Glycoproteome-Wide Discovery of Cortical Glycoproteins That May Provide Cognitive Resilience in Older Adults.Neurology · 2024Article
- Person-specific differences in ubiquitin-proteasome mediated proteostasis in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- MicroRNA-124 conducts neuroprotective effect via inhibiting AK4/ATF3 after subarachnoid hemorrhage.Experimental brain research · 2024Article
- Cytosolic calcium: Judge, jury and executioner of neurodegeneration in Alzheimer's disease and beyond.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Proteome alterations in human autopsy tissues in relation to time after death.Cellular and molecular life sciences : CMLS · 2023Article
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Authors and funding
11 authors at 1 institution in 1 country.
Lei YuFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York. lei_yu@rush.edu.ORCID 0000-0002-7176-1152
Yi-Chen HsiehFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.
Richard V PearseFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.
Yanling WangFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.
Vladislav A PetyukFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.ORCID 0000-0003-4076-151X
Julie A SchneiderFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.
Aron S BuchmanFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.ORCID 0000-0002-6426-2742
Nicholas T SeyfriedFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.ORCID 0000-0002-4507-624X
Philip L De JagerFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.ORCID 0000-0002-8057-2505
Tracy L Young-PearseFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.
David A BennettFrom the Rush Alzheimer's Disease Center (L.Y., Y.W., J.A.S., A.S.B., D.A.B.) and Department of Neurological Sciences (L.Y., Y.W., J.A.S., A.S.B., D.A.B.), Rush University Medical Center, Chicago, IL; Ann Romney Center for Neurologic Diseases (Y.H., R.V.P., T.L.P.), Department of Neurology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School (Y.H., R.V.P., T.L.P.), Boston, MA; Pacific Northwest National Laboratory (V.A.P.), Richland, WA; Department of Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Center for Translational and Computational Neuroimmunology (P.L.D.), Department of Neurology & Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York.ORCID 0000-0003-3689-554X
Brigham and Women's Hospital · US
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
$21.4MMulti-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
$13.7MCharacterizing TDP-43 related hippocampal degeneration and memory loss in agingR01AG067482 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI SCHNEIDER, JULIE A. · 2020 to 2024
$6.8MRisk Factors, Pathology, and Clinical Expressions of ADRF1AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2014 to 2014
$6.0MProbing Heterogeneity of Alzheimer's Disease Using iPSCsR01AG055909 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy L YOUNG-PEARSE · 2018 to 2026
$5.7MCell and Molecular Consequences of Alzheimer's Disease Genetic Variants on BBB Integrity and FunctionRF1NS117446 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI YOUNG-PEARSE, TRACY L · 2020 to 2020
$3.6MNIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG055909NIA NIH HHS R01 AG067482NIA NIH HHS RF1 AG015819NIA NIH HHS U01 AG061356NINDS NIH HHS RF1 NS117446
Abstract
BACKGROUND AND
objectivesIdentifying protein targets that provide cognitive reserve is a strategy to prevent and treat Alzheimer disease and Alzheimer disease related dementias (AD/ADRD). Previous studies using bulk human brain tissue reported 12 proteins associated with cognitive reserve. This study examined whether the same proteins from induced neurons (iNs) are associated with cognitive reserve of their human donors.
methodsInduced pluripotent stem cell (iPSC) lines were generated from cryopreserved peripheral blood mononuclear cells of older adults who were autopsied as part of the Religious Orders Study or Rush Memory and Aging Project. Neurons were induced from iPSCs using a standard neurogenin2 protocol. Tandem mass tag proteomics analyses were conducted on iNs day 21. Cognitive reserve of their human donors was measured as person-specific slopes of cognitive change not accounted for by common neuropathologies.
resultsThe 53 human donors died at a mean age of 91 years, all were non-Latino White, and 36 (67.9%) were female. Eighteen were diagnosed with Alzheimer dementia proximate to death, and 34 had pathologic AD diagnosis at autopsy. Approximately 60% of the donors had above-average cognitive reserve such that their cognition declined slower than an average person with comparable burdens of neuropathologies. Eight of the 12 candidate proteins were quantified in iNs proteomics analyses. Higher adenylate kinase 4 (AK4) expression in iNs was associated with lower cognitive reserve, consistent with the previous report for brain AK4 expression. DISCUSSION: By replicating cortical protein associations with cognitive reserve in human iNs, these data provide a valuable molecular readout for studying complex clinical phenotypes such as cognitive reserve in a dish.
Indexed as
Alzheimer DiseaseCognitive ReserveAgedAged, 80 and overAutopsyBrainFemaleHumansLeukocytes, MononuclearMaleNeuronsStem Cells
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