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Cited by 29Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeuroscience and Neuropharmacology Research

APOE ε4 is associated with decreased synaptic density in cognitively impaired participants

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He, Kun, Li, Binyin, Wang, Jie, Wang, Ying, You, Zhiwen, Chen, Xing, Chen, Haijuan, Li, Junpeng +8 more·2024·Alzheimer's & Dementia
DOI 10.1002/alz.13775PMC PMC11095422
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Abstract

INTRODUCTION: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants. METHODS: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18 F‐florbetapir and synaptic density PET with 18 F‐SynVesT‐1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4‐associated synaptic density loss were analyzed. RESULTS: Compared with non‐carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aβ) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype. DISCUSSION: The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers.

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Authors
He, K., Li, B., Wang, J., Wang, Y., You, Z., Chen, X., Chen, H., Li, J., Huang, Q., Guo, Q., Huang, Y. H., Guan, Y., Chen, K., Zhao, J., Deng, Y., & Xie, F.
Affiliations
  • Fudan University (CN)
  • Shanghai Jiao Tong University (CN)
  • Tongji University (CN)
  • Yale University (US)
  • University of Arizona (US)
Corresponding author
Xie, Fang
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2024-03-13
Volume
20
Issue
5
Pages
3157-3166
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.13775
PMC
PMC11095422
OpenAlex
W4392741428
Cited by
29
References
4
Citations by year
2026: 7 · 2025: 15 · 2024: 7
FWCI
8.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Key Research and Development Program of China (2016YFC1306305, 2018YFE0203600)
  • National Natural Science Foundation of China (81801752, 82171473, 82271441, 82201583)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
APOE ε4, synaptic density
MeSH terms
Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Brain, Female, Genotype, Humans, Male, Middle Aged, Synapses, Biomarkers, Amyloid beta-Peptides, tau Proteins, Positron-Emission Tomography, Apolipoprotein E4, Cognitive Dysfunction

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