Evidence map›Paper›PMID 41999218›Full record

ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2026

Proteome-wide association study of cortical proteins that may provide resilience for late-life disability.

Brittney S Lange-Maia, Ricardo A Vialle, Tianhao Wang, Andrea R Zammit, Jose Farfel, Nicholas T Seyfried, David A Bennett, Aron S Buchman

Abstract read
In one paragraph

Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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

8 authors.

Brittney S Lange-MaiaRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States.ORCID 0000-0001-6642-7558
Ricardo A VialleRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States.
Tianhao WangRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States.
Andrea R ZammitRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States.ORCID 0000-0002-2749-1239
Jose FarfelRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States.
Nicholas T SeyfriedDepartment of Biochemistry, Emory University, Atlanta, Georgia, United States.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States.ORCID 0000-0003-3689-554X
Aron S BuchmanRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States.ORCID 0000-0002-6426-2742

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
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
Identifying resilience proteins in key motor tissues that drive motor and cognitive decline and offset the negative effects of ADRD pathologies within and outside the brainR01AG075728 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI ARON S BUCHMAN · 2022 to 2026
$6.9M
Risk Factors, Pathology, and Clinical Expressions of ADRF1AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2014 to 2014
$6.0M
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
National Institute on Aging at the National Institutes of Health P30AG10161National Institute on Aging at the National Institutes of Health P30AG72975National Institute on Aging at the National Institutes of Health R01AG015819National Institute on Aging at the National Institutes of Health R01AG075728National Institute on Aging at the National Institutes of Health R01AG17917National Institute on Aging at the National Institutes of Health R01AG79133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG075728NIA NIH HHS R01 AG079133NIA NIH HHS RF1 AG015819
6 · The paper itself

Abstract

Disabilities are common and untreatable in many older adults. This proteome-wide discovery study identified cortical proteins that may provide resilience for disabilities in older adults. Participants were 850 decedents (mean age 89.3 years [SD: 6.6] at death, 67% female) from 2 longitudinal cohort studies with proteome-wide data collected from the dorsal lateral prefrontal cortex, indices of 10 Alzheimer's disease and related dementia (ADRD) pathologies, and measures of mobility disability, instrumental activities of daily living (IADLs), and activities of daily living (ADLs) prior to death. Linear regression models adjusting for demographics identified proteins related to each disability phenotype correcting for multiple comparisons (p < 5 × 10-6). Resilience proteins-operationalized as proteins related to residual disability after adjusting for ADRD pathologies-were aggregated into resilience index scores for each disability instrument and their associations with adverse health outcomes were tested. Exploratory functional enrichment analyses identified molecular pathways associated with resilience proteins. We identified 12 resilience proteins related to mobility disability, 215 for IADL and 291 for ADL disability. Models with resilience index scores accounted for an additional 2.7%, 3.3%, and 3.5% of the variance of mobility, IADL, and ADL disability, respectively, compared to 1.7%, 2.7%, and 2.0%, for ADRD pathologies. In exploratory analyses, key enriched Gene Ontology terms were predominantly related to mitochondrial function. Further work targeting these cortical proteins is needed to demonstrate that they provide resilience for disability in older adults and can facilitate functional independence in old age, though future work is needed to demonstrate protective mechanisms. Ultimately, targeting these proteins may lead to therapies that maintain functional independence in aging adults.

Indexed as

AgingPersons with DisabilitiesProteomeActivities of Daily LivingAgedAged, 80 and overAlzheimer DiseaseDisability EvaluationFemaleHumansLongitudinal StudiesMaleMobility LimitationProteomeAlzheimer's disease and related dementiapathologiesFunctional declineMobilityResilience proteins

Identifiers

PMID41999218
PMCPMC13650994

What Socratic holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.