Cholesterol content in peripheral blood cells of patients with Alzheimer's disease

Abstract

Background Alzheimer's disease (AD) is the most frequent degenerative dementia, with a prevalence expected to increase in coming years. Deposits of amyloid and hyperphosphorylated TAU protein constitute the characteristic pathological findings of the disease, although its etiology in sporadic cases is still unknown. Cholesterol metabolism has been related to AD through multiple evidences. Filipin is a macrolide that binds to cholesterol and allows its quantification. We consider assessing whether there are differences in cholesterol content determined by Filipin’s fluorescence (FF) in peripheral blood mononuclear cells (PBMCs) of patients with AD and healthy controls. Method Cross‐sectional study.Patients diagnosed with AD at different stages with support of biomarkers in cerebrospinal fluid (CSF) and cognitively healthy controls were included. PBMCs obtained from whole blood were co stained with Filipin and antibodies specific for several leucocyte subpopulations (CD8, CD4, CD11b, CD19, CD14 and CD16).FF was measured by flow cytometry in PBMCs and in different subpopulations. Results N=61 (51 AD,10 controls);When the whole PBMCs were compared, no significant differences in filipin fluorescence among diagnostic groups were observed (AD 1280, controls 1218.9; p=0.65). However, subpopulation analysis revealed significant decrease in cholesterol content in CD14+ cells of patients with AD (AD 2623.9, controls 4433.2; p = 0.007). Differences in cholesterol content in this CD14+ subpopulation were also significant in ApoE4 carriers (2427.1 in carriers, 3130.43 non‐carriers, p=0.017) Conclusions Cholesterol content of CD14+ peripheral blood mononuclear cells could be a neurodegeneration biomarker and it could be related with AD,which supports the involvement of cellular cholesterol homeostasis in the pathophysiology of the disease.