The association between circulating CD34+CD133+ endothelial progenitor cells and reduced risk of Alzheimer’s disease in the Framingham Heart Study-Reference-Cited by-同舟云学术

The association between circulating CD34+CD133+ endothelial progenitor cells and reduced risk of Alzheimer’s disease in the Framingham Heart Study

Published:2024-04-12 Issue: Volume: Page:193-214
ISSN:2692-3106
Container-title:Exploration of Medicine
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Author:

Wang Yixuan¹,Huang Jinghan²^ORCID,Ang Ting Fang Alvin³^ORCID,Zhu Yibo¹^ORCID,Tao Qiushan⁴,Mez Jesse⁵^ORCID,Alosco Michael⁶,Denis Gerald V.⁷^ORCID,Belkina Anna⁸^ORCID,Gurnani Ashita⁹,Ross Mark¹⁰,Gong Bin¹¹,Han Jingyan¹²^ORCID,Lunetta Kathryn L.¹³^ORCID,Stein Thor D.¹⁴^ORCID,Au Rhoda^ORCID,Farrer Lindsay A.^ORCID,Zhang Xiaoling¹⁵^ORCID,Qiu Wei Qiao¹⁶

Affiliation:

1. Biomedical Genetics, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

2. Biomedical Genetics, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China

3. Department of Anatomy & Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Alzheimer’s Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

4. Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

5. Alzheimer’s Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Framingham Heart Study, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

6. Alzheimer’s Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

7. Hematology & Medical Oncology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

8. Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

9. Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Framingham Heart Study, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

10. School of Energy, Geosciences, Infrastructure and Society, Institute of Life and Earth Sciences, Heriot-Watt University, EH14 4AS Edinburgh, UK

11. Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA

12. Vascular Biology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

13. Departments of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA

14. Alzheimer’s Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Pathology & Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; VA Boston Healthcare System, Boston, MA 02132, USA

15. Biomedical Genetics, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Departments of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA

16. Alzheimer’s Disease Research Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Pharmacology, Physiology and Biophysics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA; Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118, USA

Abstract

Aim: Endothelial dysfunction has been associated with both cerebrovascular pathology and Alzheimer’s disease (AD). However, the connection between circulating endothelial cells and the risk of AD remains uncertain. The objective was to leverage data from the Framingham Heart Study to investigate various circulating endothelial subtypes and their potential correlations with the risk of AD. Methods: The study conducted data analyses using Cox proportional hazard regression and linear regression methods. Additionally, genome-wide association study (GWAS) was carried out to further explore the data. Results: Among the eleven distinct circulating endothelial subtypes, only circulating endothelial progenitor cells (EPCs) expressing CD34+CD133+ were found to be negatively and dose-dependently associated with reduced AD risk. This association persisted even after adjusting for age, sex, years of education, apolipoprotein E (APOE) ε4 status, and various vascular diseases. Particularly noteworthy was the significant association observed in individuals with hypertension and cerebral microbleeds. Consistently, positive associations were identified between CD34+CD133+ EPCs and specific brain regions, such as higher proportions of circulating CD34+CD133+ cells correlating with increased volumes of white matter and the hippocampus. Additionally, a GWAS study unveiled that CD34+CD133+ cells influenced AD risk specifically in individuals with homozygous genotypes for variants in two stem cell-related genes: kirre like nephrin family adhesion molecule 3 (KIRREL3, rs580382 CC and rs4144611 TT) and exocyst complex component 6B (EXOC6B, rs61619102 CC). Conclusions: The findings suggest that circulating CD34+CD133+ EPCs possess a protective effect and may offer a new therapeutic avenue for AD, especially in individuals with vascular pathology and those carrying specific genotypes of KIRREL3 and EXOC6B genes.

Funder

National Institute on Aging

National Heart, Lung, and Blood Institute

Publisher

Open Exploration Publishing

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