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Basic Science and Pathogenesis.

Wei Zhao1,2, Zheng Li2, Jennifer A Smith1,2

  • 1University of Michigan Institute for Social Research, Ann Arbor, MI, USA.

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|December 23, 2025
PubMed
Summary
This summary is machine-generated.

Genetic analysis in South Asians reveals MAPT gene variants are associated with Alzheimer's disease (AD) biomarkers, including total tau (tTau) and phosphorylated tau (pTau181). APOE-e4 may modify these associations, suggesting complex genetic influences on AD pathology.

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Area of Science:

  • Neuroscience
  • Genetics
  • Biomarkers

Background:

  • Alzheimer's disease (AD) is linked to abnormal protein levels in blood, serving as biomarkers.
  • Understanding AD's genetic basis in South Asians requires studying genetic variants and their association with AD biomarkers.

Purpose of the Study:

  • To investigate the association between single nucleotide polymorphisms (SNPs) and seven AD biomarkers in South Asians.
  • To explore the genetic architecture of AD and its biomarkers within the South Asian population.

Main Methods:

  • SNP-based association analysis was conducted on 152 AD-associated and 9 AD biomarker-associated SNPs with seven blood-based AD biomarkers.
  • Statistical models adjusted for covariates including age, sex, and genetic principal components.
  • Follow-up haplotype analysis was performed on identified loci, including MAPT and APOE-e4 stratification.

Main Results:

  • SNPs in MAPT (rs199515_C, rs242557_A) showed significant associations with total tau (tTau) and phosphorylated tau (pTau181).
  • APOE-e4 (rs429358_C) was associated with the amyloid beta 42/40 ratio.
  • Haplotype analysis revealed specific MAPT haplotypes (H1j, H2, H1r, H1b, H1c, H1o) associated with varying tTau levels, with APOE-e4 modifying these associations.

Conclusions:

  • The MAPT gene plays a significant role in tau pathology among South Asians.
  • Observed associations may not be solely driven by known risk haplotypes and appear to be modified by APOE-e4.
  • Further research into MAPT haplotype structure in this population is recommended.