Evidence map›Paper›PMID 38165375›Full record

ArticleNeurology2024

Proteome-wide Analyses Identified Cortical Proteins Associated With Resilience for Varied Cognitive Abilities.

Andrea R Zammit, Hans-Ulrich Klein, Lei Yu, Allan I Levey, Nicholas T Seyfried, Aliza P Wingo, Thomas S Wingo, Julie A Schneider, David A Bennett, Aron S Buchman

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In one paragraph

Article in Neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  5. Article
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Andrea R ZammitFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.
Hans-Ulrich KleinFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.
Lei YuFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.ORCID 0000-0002-7176-1152
Allan I LeveyFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.
Nicholas T SeyfriedFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.ORCID 0000-0002-4507-624X
Aliza P WingoFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.
Thomas S WingoFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.ORCID 0000-0002-7679-6282
Julie A SchneiderFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.
David A BennettFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.ORCID 0000-0003-3689-554X
Aron S BuchmanFrom the Rush Alzheimer's Disease Center (A.R.Z., L.Y., J.A.S., D.A.B., A.S.B.), and Departments of Psychiatry and Behavioral Sciences (A.R.Z.), Neurological Sciences (L.Y., J.A.S., D.A.B., A.S.B.), and Pathology (J.A.S.), Rush University Medical Center, Chicago, IL; Department of Neurology (H.-U.K.), Columbia University Medical Center, New York, NY; Departments of Neurology (A.I.L., N.T.S., T.S.W.) Psychiatry (A.P.W.), and Human Genetics (T.S.W.), and the Goizueta Alzheimer's Disease Center (T.S.W.), Emory University School of Medicine, Atlanta, GA; Department of Biochemistry (N.T.S.), Emory University, Atlanta, GA; and Division of Mental Health (A.P.W.), Atlanta VA Medical Center, Decatur, GA.ORCID 0000-0002-6426-2742

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BARNES, LISA L · 1991 to 2020
$49.1M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Supplement to AMP-AD Brain Proteomic Network Enhancement, Validation and Translation into CSF BiomarkersU01AG061357 · NIA · EMORY UNIVERSITY · PI LEVEY, ALLAN I, SEYFRIED, NICHOLAS THOMAS · 2018 to 2022
$9.1M
The brain multi-omic approach to identify key molecular drivers of neuropsychiatric symptoms in Alzheimer's dementiaR01AG072120 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Aliza Pham Wingo, Thomas Spurgeon Wingo · 2022 to 2026
$4.3M
Integrative genomic, transcriptomic, and proteomic analyses to investigate sex-specific differences in Alzheimer's DiseaseR01AG075827 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Aliza Pham Wingo, Thomas Spurgeon Wingo · 2022 to 2026
$3.7M
Air pollution and early signs of dementiaR01AG079170 · NIA · EMORY UNIVERSITY · PI Anke Huels, Thomas Spurgeon Wingo · 2022 to 2026
$3.6M
Thinking about walking: Can digital phenotyping of mobility improve the prediction of Alzheimer's dementia and inform on the pathologies and proteins contributing to this association?R01AG079133 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI ARON S BUCHMAN · 2022 to 2026
$3.5M
Elucidating the molecular drivers of impaired mobility within and outside the CNS in Alzheimer’s disease and related disordersR01AG059732 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BUCHMAN, ARON S · 2019 to 2023
$2.8M
Application of latent and integrative approaches to understand the spectrum of cognitive agingK01AG054700 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI ZAMMIT, ANDREA ROSE · 2017 to 2021
$653k
NIA NIH HHS K01 AG054700NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG059732NIA NIH HHS R01 AG072120NIA NIH HHS R01 AG075827NIA NIH HHS R01 AG079133NIA NIH HHS R01 AG17917NIA NIH HHS R01 AG75728NIA NIH HHS U01 AG061357NIA NIH HHS U01 AG61356
6 · The paper itself

Abstract

BACKGROUND AND

objectivesPrior work suggests that cognitive resilience may contribute to the heterogeneity of cognitive decline. This study examined whether distinct cortical proteins provide resilience for different cognitive abilities.

methodsParticipants were from the Religious Orders Study or the Rush Memory and Aging Project who had undergone annual assessments of 5 cognitive abilities and postmortem assessment of 9 Alzheimer disease and related dementia (ADRD) pathologies. Proteome-wide examination of the dorsolateral prefrontal cortex using tandem mass tag and liquid chromatography-mass spectrometry yielded 8,425 high-abundance proteins. We applied linear mixed-effect models to quantify residual cognitive change (cognitive resilience) of 5 cognitive abilities by regressing out cognitive decline related to age, sex, education, and indices of ADRD pathologies. Then we added terms for each of the individual proteins to identify cognitive resilience proteins associated with the different cognitive abilities.

resultsWe included 604 decedents (69% female; mean age at death = 89 years) with proteomic data. A total of 47 cortical proteins that provide cognitive resilience were identified: 22 were associated with specific cognitive abilities, and 25 were common to at least 2 cognitive abilities. NRN1 was the only protein that was associated with more than 2 cognitive abilities (semantic memory: estimate = 0.020, SE = 0.004, DISCUSSION: This study identified cortical proteins associated with various cognitive abilities. Differential associations across abilities may reflect distinct underlying biological pathways. These data provide potential high-value targets for further mechanistic and drug discovery studies to develop targeted treatments to prevent loss of cognition.

Indexed as

Memory, EpisodicNeuropeptidesResilience, PsychologicalAged, 80 and overCognitionFemaleGPI-Linked ProteinsHumansMaleProteomeProteomicsGPI-Linked ProteinsNeuropeptidesNRN1 protein, humanProteome

Identifiers

PMID38165375
PMCPMC10834136

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