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Basic Science and Pathogenesis.

Alvin G Thomas1, Laura Raffield2, Keenan A Walker3

  • 1Washington University in St. Louis, St. Louis, MO, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 23, 2025
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Summary
This summary is machine-generated.

Cognitive resilience in older adults is linked to specific blood proteins, offering new insights into brain health. Understanding these protein pathways may reveal mechanisms underlying resilience to Alzheimer's disease and related disorders.

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Area of Science:

  • Neuroscience
  • Proteomics
  • Aging Research

Background:

  • Cognitive function varies in older adults despite similar Alzheimer's disease and related disorders (ADRD) biomarker levels.
  • Cognitive resilience, the ability to maintain cognitive function, has unclear biological underpinnings.

Purpose of the Study:

  • To investigate the association between circulating plasma proteins and cognitive resilience in older adults.
  • To identify specific protein markers and pathways related to cognitive resilience.

Main Methods:

  • Utilized SomaScan proteomic data from 1,590 Atherosclerosis Risk in Communities (ARIC) study participants.
  • Defined cognitive resilience using residuals from cognitive factor scores regressed on demographic and MRI features.
  • Employed linear regression to analyze associations between 4,955 proteins and cognitive resilience.

Main Results:

  • Identified 30 proteins significantly associated with cognitive resilience overall and within race-sex groups.
  • Pathway analysis revealed involvement of neuroprotective (DHCR24) and biopeptide clearance (THOP1) pathways.
  • Highlighted the role of the brain's immune system and glial cells in cognitive resilience.

Conclusions:

  • Demonstrated the feasibility of studying cognitive resilience within a cardiovascular cohort.
  • Suggests further research through proteomic and genomic meta-analyses for deeper insights.