Chen SH, Tian DY, Shen YY, Cheng Y, Fan DY, Sun HL, He CY, Sun PY, Bu XL, Zeng F, Liu J, Deng J, Xu ZQ, Chen Y and Wang YJ

Transl Psychiatry 10, 423 (2020).

DOI: https://doi.org/10.1038/s41398-020-01113-9

Abstract

Deficits in the clearance of amyloid β-protein (Aβ) play a pivotal role in the pathogenesis of sporadic Alzheimer’s disease (AD). The roles of blood monocytes in the development of AD remain unclear. In this study, we sought to investigate the alterations in the Aβ phagocytosis function of peripheral monocytes during aging and in AD patients. A total of 104 cognitively normal participants aged 22–89 years, 24 AD patients, 25 age- and sex-matched cognitively normal (CN) subjects, 15 Parkinson’s disease patients (PD), and 15 age- and sex-matched CN subjects were recruited. The Aβ uptake by blood monocytes was measured and its alteration during aging and in AD patients were investigated. Aβ_1-42 uptake by monocytes decreased during aging and further decreased in AD but not in PD patients. Aβ_1-42 uptake by monocytes was associated with Aβ_1-42 levels in the blood. Among the Aβ uptake-related receptors and enzymes, the expression of Toll-like receptor 2 (TLR2) was reduced in monocytes from AD patients. Our findings suggest that monocytes regulate the blood levels of Aβ and might be involved in the development of AD. The recovery of the Aβ uptake function by blood monocytes represents a potential therapeutic strategy for AD.