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Basic Science and Pathogenesis.

Justina P Tavana1, Maegan Leary1, James E Galvin2

  • 1Brigham Young University, Provo, UT, USA.

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Summary
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APOE ε2 and ε4 alleles do not predict mild cognitive impairment (MCI) in Native Hawaiian and Pacific Islander (NHPI) populations. This study highlights the need for diverse datasets in Alzheimer's disease (AD) research.

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Area of Science:

  • Neuroscience
  • Genetics
  • Public Health

Background:

  • Alzheimer's disease (AD) research datasets are predominantly White, limiting clinical utility and potentially causing population disparities.
  • Native Hawaiian and Pacific Islander (NHPI) populations exhibit higher AD risk, earlier onset, and worse cognitive scores.
  • NHPIs are significantly underrepresented in major AD research repositories.

Purpose of the Study:

  • To investigate the association of APOE ε2 and ε4 alleles with mild cognitive impairment (MCI) in NHPI populations.
  • To address the lack of genetic data for NHPIs in AD research.
  • To compare APOE SNP frequencies in NHPIs with other global populations.

Main Methods:

  • Recruited approximately 2,000 older NHPIs across Utah, Hawaii, American Samoa, and Tonga.
  • Collected biospecimens and administered the AD8 cognitive impairment test.
  • Genotyped APOE ε2 (rs7412) and ε4 (rs429358) SNPs, analyzing frequencies and association with MCI.

Main Results:

  • The cohort comprised 1,367 NHPI adults, with 1,325 of single ancestry from diverse Polynesian groups.
  • NHPIs have a comparable ε2 minor allele frequency (MAF) but a doubled ε4 MAF (∼25%) versus other populations.
  • Neither APOE ε2 nor ε4 was significantly correlated with MCI in this cohort (p-values ≈ 1).

Conclusions:

  • APOE ε2 and ε4 alleles do not appear to predict MCI in Native Hawaiian and Pacific Islander populations.
  • Despite a relatively small cohort size, the study had sufficient power to detect effect sizes similar to those in other populations.
  • Findings align with research in other Indigenous populations showing no significant APOE-dementia correlation.