Increased circulating endothelial progenitor cells as a biomarker for cerebral microvascular pathology in cognitively normal older adults: Molecular and cell biology/vascular factors. (7th December 2020)

• Record Type: Journal Article
• Authors: Kapoor, Arunima; Gaubert, Aimee; Marshall, Anisa J.; Meier, Irene B.; Yew, Belinda; Ho, Jean K.; Blanken, Anna E.; Dutt, Shubir; Sible, Isabel J.; Li, Yanrong; Jang, Jung Yun; Brickman, Adam M.; Rodgers, Kathleen E.; Nation, Daniel A.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.045527
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Cerebral microvascular pathologies—including white matter lesions, microbleeds and lacunes—are associated with increased risk of vascular dementia and Alzheimer's disease. Despite the role of cerebral microvascular pathological changes in cognitive decline, such changes often remain asymptomatic until pathology progresses to severe stages, and early‐stage markers of cerebrovascular changes are lacking. Elevated levels of circulating endothelial progenitor cells (EPCs) have previously been observed in response to vascular injury and may represent a protective vascular mechanism. However, few previous studies have examined levels of circulating EPCs in older adults with signs of cerebral microvascular pathology. Method: Independently living older adults (ages 55‐90) free of dementia or clinical stroke were recruited from the community and underwent venipuncture and brain MRI. Mononuclear cells were isolated and stained for EPC surface markers CD34, CD133 and CD309. Circulating EPCs were quantified by flow cytometry as the number of cells in the lymphocyte gate positively expressing all three markers (CD34+CD133+CD309+). MRI changes thought to represent microvascular pathologies (white matter hyperintensities, cerebral microbleeds and lacunes) were evaluated and total microvascular disease load was determined using a previously validated score. Result: Fifty‐three older adults (mean age = 69.3 years (SD = 7.5); education = 15.7 years (SD = 2.8); 19 (35.8%) male) were included in this preliminary analysis. Moderate/severe white matter hyperintensity burden was identified by Fazekas scale in 35.8% of participants, small lacunes were identified in 15.1% and microbleeds in 5.7%. Linear regression analyses revealed that older adults with more circulating EPCs exhibited greater total microvascular pathology load (p = .034), after accounting for age, sex and education. Conclusion: Our preliminary findings suggest a role for circulating EPCs as an early‐stage biomarker for cerebral microvascular pathology in older adults free of dementia or stroke symptoms. Novel diagnostic approaches to recognize microvascular changes are needed to identify individuals at risk of dementia before the onset of irreversible cognitive impairment. Longitudinal studies examining the association between EPCs and dementia risk are warranted to further explore the utility of EPCs as a biomarker for cerebral microvascular disease.