# Endothelial progenitor cells and cerebral small vessel disease in APOE4 carriers

## TL;DR

APOE4 carriers show early cerebrovascular issues, and higher levels of endothelial progenitor cells may help protect brain vessels before cognitive decline.

## Contribution

This study identifies a link between endothelial progenitor cell counts and reduced cerebral small vessel disease in APOE4 carriers.

## Key findings

- Higher EPC colony count is associated with lower cerebral small vessel disease burden in APOE4 carriers.
- EPC colony count correlates with reduced white matter hyperintensity volume in APOE4 carriers.
- EPCs may reflect protective mechanisms in cerebrovascular function before cognitive decline in APOE4 carriers.

## Abstract

•APOE4 carriers exhibit cerebrovascular dysfunction.•Endothelial progenitor cells (EPC) represent cell populations involved in facilitating vascular repair.•In APOE4 carriers, EPC colony count is associated with cerebral small vessel disease.•EPC colony count may indicate activation of mechanisms which protect cerebrovascular function in APOE4 carriers prior to the development of cognitive decline.

APOE4 carriers exhibit cerebrovascular dysfunction.

Endothelial progenitor cells (EPC) represent cell populations involved in facilitating vascular repair.

In APOE4 carriers, EPC colony count is associated with cerebral small vessel disease.

EPC colony count may indicate activation of mechanisms which protect cerebrovascular function in APOE4 carriers prior to the development of cognitive decline.

APOE4 carriers at genetic risk for Alzheimer's disease exhibit early cerebrovascular dysfunction, which may be triggered by endothelial dysfunction. Endothelial progenitor cells (EPCs) represent cell populations involved in promoting angiogenesis and facilitating vascular repair in response to injury. We examined whether elevated EPCs are associated with lower cerebral small vessel disease burden in APOE4 carriers prior to cognitive decline. Independently living older adults (N = 109, mean age = 70.5 years; SD = 7.9; 34.9 % male) free of dementia or clinical stroke underwent brain MRI and venipuncture. Small vessel disease was determined using a validated scale. White matter hyperintensity (WMH) volume was determined using the lesion segmentation toolbox. PBMCs were cultured and EPCs were defined as number of colony forming units in vitro. Regression analysis revealed an association between average number of EPC colonies and lower small vessel disease load (p = .026) and WMH volume (p = .002), in APOE4 carriers. Findings suggest that EPC colony count may indicate activation of mechanisms which protect cerebrovascular function in APOE4 carriers prior to the development of cognitive decline.