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Increased circulating endothelial progenitor cells as a biomarker for cerebral microvascular pathology in cognitively normal older adults
Author(s) -
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.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045527
Subject(s) - medicine , hyperintensity , pathology , dementia , asymptomatic , vascular dementia , cognitive decline , stroke (engine) , biomarker , progenitor cell , cardiology , magnetic resonance imaging , disease , stem cell , biology , radiology , mechanical engineering , biochemistry , genetics , engineering
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.