Reduced Effect of APOE4 on White Matter Microstructure in an American Indian Community

René Labounek; M. Matheson; Corey A. Strong; Ashley Petersen; Annamarie Hill; Ann J. Robertson; Adam Hansen; Adam D. Block; J. Neil Henderson; Igor Nestrašil; Christophe Lenglet; William G. Mantyh

doi:10.1212/nxg.0000000000200418

July 16, 2026Neurology GeneticsOpen Access

Reduced Effect of APOE4 on White Matter Microstructure in an American Indian Community

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Key Points

This study investigates the relationship between the APOE4 allele and white matter microstructure in an American Indian community.
Examined white matter microstructure among Elders in the American Indian community
Focus on those carrying the APOE4 allele
Utilized neuroimaging techniques to assess brain health
APOE4's effect on white matter microstructure was significantly reduced in the American Indian population examined
Findings suggest a unique ancestry-dependent relationship affecting Alzheimer disease risk
Results indicate that traditional risks associated with APOE4 may not directly apply to this community

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Implication

Examines white matter health in American Indian Elders carrying APOE4, suggesting altered risk dynamics.

Abstract

Apolipoprotein E4 (APOE4) is central to Alzheimer disease (AD) personalized medicine, yet its link to AD is highly ancestry-dependent. Emerging evidence suggests an attenuated risk of APOE4 on brain health in American Indian (AI) participants. This study examines white matter microstructure, an early indicator of brain health deterioration, among tribal Elders carrying the APOE4 allele.

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Cite This Study

Labounek et al. (2026) studied this question.

synapsesocial.com/papers/6a5b16f018557b26c2039487 https://doi.org/10.1212/nxg.0000000000200418

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Reduced Effect of APOE4 on White Matter Microstructure in an American Indian Community

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Abstract

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Cite This Study

Reduced Effect of APOE4 on White Matter Microstructure in an American Indian Community

Key Points

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Implication

Abstract

Discussion

Cite This Study

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