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Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Filippos Anagnostakis1,2, Mehrshad Saadatinia1, Sarah Ko1

  • 1Laboratory of AI and Biomedical Science (LABS), Columbia University, New York, NY, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
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Summary
This summary is machine-generated.

This study reveals that the SPARE-AD imaging signature for Alzheimer's disease brain atrophy increases with age and is influenced by sex and APOE ε4 allele status. Brain biological age gap significantly correlates with SPARE-AD across all participants.

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Area of Science:

  • Neuroimaging
  • Machine Learning in Medicine
  • Alzheimer's Disease Research

Background:

  • Investigated sex differences in the SPARE-AD (Signature for the Progression of Alzheimer’s Disease) imaging signature.
  • Examined the relationship between SPARE-AD, age, APOE ε4 allele, and multi-organ biological age gap (BAG).

Purpose of the Study:

  • To determine sex-specific patterns in brain atrophy signatures related to Alzheimer's disease.
  • To assess the influence of genetic factors (APOE ε4) and biological age on these signatures.

Main Methods:

  • Utilized data from 53,622 cognitively normal participants from the iSTAGING and MULTI consortia.
  • Employed a support vector machine (SPARE-AD model) to quantify brain atrophy.
  • Applied generalized linear models and ANCOVA to analyze sex differences, BAG associations, and APOE ε4 effects.

Main Results:

  • SPARE-AD scores increased with age and were positively associated with the number of APOE ε4 alleles.
  • Sex differences in SPARE-AD were observed, with higher scores in women at younger ages and in men at older ages.
  • The brain BAG showed the strongest association with SPARE-AD, followed by other BAGs significant in men but not women.

Conclusions:

  • SPARE-AD demonstrates age- and sex-dependent trajectories, highlighting differential aging patterns in the brain.
  • The APOE ε4 allele influences SPARE-AD, particularly in men, suggesting sex-specific genetic effects on neurodegeneration.
  • Biological age, especially brain age, is a critical factor associated with brain atrophy signatures indicative of Alzheimer's disease risk.