Increased Circulating Progenitor Cells in Alzheimer's Disease Patients with Moderate to Severe Dementia: Evidence for Vascular Repair and Tissue Regeneration?

Abstract

Cerebrovascular dysfunction is a common finding in patients with Alzheimer's disease (AD) and may contribute to cognitive decline. Abundant evidence suggests that vascular and neuronal repair mechanisms are mediated by circulating progenitor cells in vivo. Whether CD34⁺ and, specifically, CD34⁺/CD133⁺ progenitor cells are involved in the pathophysiology of AD is poorly understood so far. In the present study, peripheral blood concentrations of circulating CD34⁺/CD133⁺ and CD34⁺ progenitor cells were measured in 45 AD patients and in 30 healthy elderly controls by flow cytometry. The severity of dementia was assessed by Mini-Mental Status Examination and Clinical Dementia Rating scale. AD patients were stratified into two groups showing mild (n = 17) and moderate to severe (n = 28) dementia. In the present study, AD patients with moderate to severe dementia, but not those with mild dementia, showed significantly increased circulating CD34⁺/CD133⁺ and CD34⁺ progenitor cells compared to healthy elderly controls independent of cardiovascular risk factors and medication. In addition, the number of circulating CD34⁺/CD133⁺ progenitor cells in AD patients was significantly inversely correlated with cognitive function, age, and plasma levels of SDF-1, the most potent chemokine for progenitor cells. Our findings suggest a stage-dependent upregulation of circulating CD34⁺/CD133⁺ and CD34⁺ progenitor cells in AD patients, which could take part in tissue healing processes of the brain in AD.