A study on the correlation between APOE gene polymorphism, white matter hyperintensities, and neuropsychiatric symptom phenotypes in Alzheimer’s disease

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The study examines the effects of APOE genotypes and white matter hyperintensities on neuropsychiatric symptoms in Alzheimer's disease patients.
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Significant cognitive and functional differences were found across APOE genotype groups, particularly with ϵ4 allele carriers showing higher agitation.
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ϵ4/ϵ4 homozygotes exhibited greater severity in delusions, agitation, irritability, and euphoria compared to other genotype groups.
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Mediation analysis indicated that white matter hyperintensities do not mediate the relationship between APOE genotype and neuropsychiatric outcomes.
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APOE genotype serves as a valuable biomarker for Alzheimer's disease risk and prognosis, particularly for neuropsychiatric symptoms.

Frontiers In Psychiatry

by Wei Fan, Ziqi Wang, Shu Wan, Man Liu, Yuanyuan Han, Xiaowei Liu, Lisi Xu, Xiaoyan Wang, Dingyi Zhang, Qingyan Cai
March 20, 2026

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