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

Marcella A Barneclo1, Nancy E Ortega2,3, Iris J Broce-Diaz4

  • 1Alzheimer's Disease Cooperative Study, La Jolla, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

The TOMM40-G allele is associated with Alzheimer's disease (AD) plasma biomarkers. Sex and APOE4 interact with TOMM40-G to influence AD risk biomarkers, suggesting complex sex-specific AD pathology.

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Area of Science:

  • Neuroscience
  • Genetics
  • Biomarker Research

Background:

  • The TOMM40 gene, specifically the G allele of SNP rs2075650 (TOMM40-G), is a known risk variant for Alzheimer's disease (AD).
  • TOMM40-G carriers may face increased AD risk due to potential mitochondrial dysfunction, neurodegeneration, and age-related diseases.
  • Limited research exists on TOMM40-G's association with plasma AD biomarkers and the moderating effects of sex and APOE4.

Purpose of the Study:

  • To investigate the association between the TOMM40-G allele and plasma AD biomarkers in cognitively unimpaired older adults.
  • To examine potential sex differences and interactions involving TOMM40-G, sex, and APOE4 in relation to AD biomarkers.
  • To explore how TOMM40-G influences levels of amyloid beta (Aβ), phosphorylated tau (ptau), GFAP, and NfL.

Main Methods:

  • Analysis of genetic and plasma biomarker data from 1,149 cognitively unimpaired older adults in the A4 cohort.
  • Investigated TOMM40-G (rs2075650) carriers versus non-carriers for differences in Aβ42, Aβ42/40, ptau181, ptau217, GFAP, and NfL.
  • Statistical models incorporated interaction terms for sex and APOE4 with the TOMM40-G allele, controlling for age and education.

Main Results:

  • TOMM40-G carriers showed altered plasma biomarkers, including increased ptau217 and decreased Aβ42/40 and Aβ42.
  • APOE4 carriers had lower Aβ42/Aβ42/40 and higher ptau181/ptau217.
  • Significant sex differences were observed for ptau217, GFAP, and Aβ42 levels. Interactions between sex and TOMM40-G affected NfL and Aβ42. Sex and APOE4 interactions influenced Aβ42 and Aβ42/40.

Conclusions:

  • The TOMM40-G risk allele is associated with distinct plasma AD biomarker profiles.
  • APOE4 and TOMM40-G may interact with sex to modulate AD biomarkers, highlighting complex sex-specific risk pathways.
  • Further research is warranted to fully elucidate sex-specific mechanisms in AD pathogenesis.