Circulating Endothelial Progenitor Cells Reduce the Risk of Alzheimer’s Disease
Circulating Endothelial Progenitor Cells Reduce the Risk of Alzheimer’s Disease
Summary Cerebrovascular damage coexists with Alzheimer’s disease (AD) pathology and increases AD risk. However, it is unclear whether endothelial progenitor cells reduce AD risk via cerebrovascular repair. By using the Framingham Heart Study (FHS) offspring cohort, which includes data on different progenitor cells, the incidence of AD dementia, peripheral and cerebrovascular pathologies, and genetic data (n = 1,566), we found that elevated numbers of circulating endothelial progenitor cells with CD34+CD133+ co-expressions had a dose-dependent association with decreased AD risk (HR = 0.67, 95% CI: 0.46-0.96, p = 0.03) after adjusting for age, sex, years of education, and APOE ε4. With stratification, this relationship was only significant among those individuals who had vascular pathologies, especially hypertension (HTN) and cerebral microbleeds (CMB), but not among those individuals who had neither peripheral nor central vascular pathologies. We applied a genome-wide association study (GWAS) and found that the number of CD34+CD133+ cells impacted AD risk depending on the homozygous genotypes of two genes: KIRREL3 rs580382 CC carriers (HR = 0.31, 95% CI: 0.17-0.57, p<0.001), KIRREL3 rs4144611 TT carriers (HR = 0.29, 95% CI: 0.15-0.57, p<0.001), and EXOC6B rs61619102 CC carriers (HR = 0.49, 95% CI: 0.31-0.75, p<0.001) after adjusting for confounders. In contrast, the relationship did not exist in their counterpart genotypes, e.g. KIRREL3 TT/CT or GG/GT carriers and EXOC6B GG/GC carriers. Our findings suggest that circulating CD34+CD133+ endothelial progenitor cells can be therapeutic in reducing AD risk in the presence of cerebrovascular pathology, especially in KIRREL3 and EXOC6B genotype carriers.
Denis Gerald V.、Ang Ting Fang Alvin、Au Rhoda、Tao Qiushan、Alosco Michael、Mez Jesse、Gong Bin、Qiu Wei Qiao、Belkina Anna、Huang Jinghan、Ross Mark、Stein Thor D.、Han Jingyan、Wang Yixuan、Zhu Yibo、Farrer Lindsay A.、Zhang Xiaoling、Lunetta Kathryn L.、Gurnani Ashita
Department of Medicine Hematology & Medical Oncology, Boston University Chobanian & Avedisian School of MedicineDepartment of Medicine Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine||Alzheimer?ˉs Disease Research Center, Boston University Chobanian & Avedisian School of MedicineDepartment of Medicine Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine||Neurology, Boston University Chobanian & Avedisian School of Medicine||Framingham Heart Study, Boston University Chobanian & Avedisian School of Medicine||Alzheimer?ˉs Disease Research Center, Boston University Chobanian & Avedisian School of Medicine||School of Energy, Geosciences, Infrastructure and Society, Institute of Life and Earth Sciences, Heriot-Watt UniversityDepartment of Medicine Pharmacology & Experimental Therapeutics, Boston University Chobanian & Avedisian School of MedicineNeurology, Boston University Chobanian & Avedisian School of Medicine||Alzheimer?ˉs Disease Research Center, Boston University Chobanian & Avedisian School of MedicineNeurology, Boston University Chobanian & Avedisian School of Medicine||Framingham Heart Study, Boston University Chobanian & Avedisian School of Medicine||Alzheimer?ˉs Disease Research Center, Boston University Chobanian & Avedisian School of MedicineDepartment of Pathology, University of Texas Medical BranchDepartment of Medicine Pharmacology & Experimental Therapeutics, Boston University Chobanian & Avedisian School of Medicine||Psychiatry, Boston University Chobanian & Avedisian School of Medicine||Alzheimer?ˉs Disease Research Center, Boston University Chobanian & Avedisian School of MedicinePathology &Laboratory Medicine, Boston University Chobanian & Avedisian School of MedicineDepartment of Medicine Biomedical Genetics, Boston University Chobanian & Avedisian School of MedicineSchool of Energy, Geosciences, Infrastructure and Society, Institute of Life and Earth Sciences, Heriot-Watt UniversityPathology &Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine||Alzheimer?ˉs Disease Research Center, Boston University Chobanian & Avedisian School of Medicine||VA Boston Healthcare SystemDepartment of Medicine Vascular Biology, Boston University Chobanian & Avedisian School of MedicineDepartment of Medicine Biomedical Genetics, Boston University Chobanian & Avedisian School of MedicineDepartment of Medicine Biomedical Genetics, Boston University Chobanian & Avedisian School of MedicineDepartment of Medicine Biomedical Genetics, Boston University Chobanian & Avedisian School of Medicine||Neurology, Boston University Chobanian & Avedisian School of Medicine||Ophthalmology, Boston University Chobanian & Avedisian School of Medicine||Framingham Heart Study, Boston University Chobanian & Avedisian School of Medicine||Alzheimer?ˉs Disease Research Center, Boston University Chobanian & Avedisian School of Medicine||Department of Biostatistics, Boston University School of Public Health||Department of Epidemiology, Boston University School of Public HealthDepartment of Medicine Biomedical Genetics, Boston University Chobanian & Avedisian School of Medicine||Department of Biostatistics, Boston University School of Public HealthDepartment of Biostatistics, Boston University School of Public HealthNeurology, Boston University Chobanian & Avedisian School of Medicine||Framingham Heart Study, Boston University Chobanian & Avedisian School of Medicine
神经病学、精神病学基础医学医学研究方法
Alzheimer’s diseaseCD34+CD133+circulating endothelial progenitor cellsvascular diseasesGWAS
Denis Gerald V.,Ang Ting Fang Alvin,Au Rhoda,Tao Qiushan,Alosco Michael,Mez Jesse,Gong Bin,Qiu Wei Qiao,Belkina Anna,Huang Jinghan,Ross Mark,Stein Thor D.,Han Jingyan,Wang Yixuan,Zhu Yibo,Farrer Lindsay A.,Zhang Xiaoling,Lunetta Kathryn L.,Gurnani Ashita.Circulating Endothelial Progenitor Cells Reduce the Risk of Alzheimer’s Disease[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2023.01.16.23284571.点此复制
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