Apolipoprotein E ε4 homozygosity exacerbates retinal and cerebral microvascular dysfunction in Alzheimer's disease: A mediation analysis of vascular contributions to cognitive decline
Apolipoprotein E (APOE) ε4 homozygosity is associated with the most severe reductions in retinal microvascular densities and elevated cerebral small vessel disease (peak width of skeletonized mean diffusivity [PSMD]) in Alzheimer's disease (AD). Vascular dysfunction (retinal and cerebral) correlates with lower Aβ42, higher p-tau217/Aβ<sub>42</sub>, and worse cognitive scores (Mini-Mental State Examination [MMSE], Montreal Cognitive Assessment [MoCA]). Mediation analysis reveals that retinal (superficial vascular complex [SVC]) and cerebral (PSMD) microvascular changes partially explain the link between APOE ε4 and cognitive decline. Findings highlight vascular pathways as potential therapeutic targets in APOE ε4 carriers to mitigate cognitive impairment.
Authors
- Caiyun Wen
- Hanyu Zhu (ORCID: https://orcid.org/0000-0002-8729-4245)
- William Robert Kwapong (ORCID: https://orcid.org/0000-0001-9633-4694)
- Jingjing Qian (ORCID: https://orcid.org/0000-0003-4624-9963)
- Jiahui Chen (ORCID: https://orcid.org/0009-0006-3847-8298)
- Xiaoqian Luan (ORCID: https://orcid.org/0000-0003-1395-4797)
- Youjie Wang (ORCID: https://orcid.org/0000-0001-7031-2972)
- B. Tang (ORCID: https://orcid.org/0000-0002-7644-5247)
- Zhen Wang (ORCID: https://orcid.org/0000-0002-8581-4649)
- Yuntao Liu (ORCID: https://orcid.org/0000-0003-4033-2133)
- Lin Cao (ORCID: https://orcid.org/0000-0001-5355-8751)
- Jianing Shen (ORCID: https://orcid.org/0000-0003-4050-0299)
- Yinhe Liu (ORCID: https://orcid.org/0000-0002-2578-6308)
- Ho Ko (ORCID: https://orcid.org/0000-0002-0254-3274)
Institutions
- Chinese University of Hong Kong (HK)
- Capital Medical University (CN)
- Sichuan University (CN)
- Wenzhou Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Quzhou City People's Hospital (CN)
- West China Hospital of Sichuan University (CN)
- Quzhou University (CN)
- Viva Biotech (China) (CN)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/alz.71000
- Citations
- 1
- Primary Topic
- Retinal Imaging and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 1.36
Funders
- Wenzhou Medical University