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

Mengna Zhang1, Guray Erus2, Yuhan Cui3

  • 1Vanderbilt Memory and Alzheimer's Center, Vanderbilt University School of Medicine, Nashville, TN, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

The APOE ε4 gene variant impacts brain atrophy patterns in Alzheimer's Disease (AD), with initial effects seen in females. However, the progression of this brain atrophy is similar in both sexes.

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Area of Science:

  • Neuroscience
  • Genetics
  • Gerontology

Background:

  • Alzheimer's Disease (AD) is a neurodegenerative disorder.
  • The APOE ε4 allele is the strongest genetic risk factor for AD.
  • APOE ε4 exhibits sex-dependent effects, posing a greater risk for females.

Purpose of the Study:

  • Investigate if APOE ε4 carrier status affects brain atrophy patterns measured by the SPARE-AD index.
  • Determine if these effects are modified by sex.

Main Methods:

  • Utilized data from 3,289 participants across four AD and cognitive aging cohorts.
  • Calculated the SPARE-AD index using a non-linear pattern classification method.
  • Employed cross-sectional and longitudinal analyses, including sex-stratified and meta-analyses.

Main Results:

  • APOE ε4 carriers exhibited higher SPARE-AD indices at baseline, significantly in females.
  • Cognitively unimpaired individuals showed slower SPARE-AD progression than those with MCI.
  • APOE ε4 carriers demonstrated accelerated SPARE-AD progression, irrespective of sex.

Conclusions:

  • APOE ε4 carrier status influences both the pattern and progression of brain atrophy.
  • Baseline effects of APOE ε4 on brain atrophy are more pronounced in females.
  • Longitudinal progression rates of brain atrophy associated with APOE ε4 are similar between sexes.