Amyloid-beta uptake by peripheral blood monocytes is reduced by ageing and Alzheimer’s disease

Background: 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, the counterparts of microglia in the periphery, 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 ageing and in AD patients. Methods: A total of 104 cognitively normal participants aged 22 to 89 years old, 22 AD patients, 22 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 were measured and its alteration during ageing and in AD were investigated. Results: Aβ 1−42 uptake by monocytes was associated with Aβ 1−42 levels in the blood. Aβ 1−42 uptake by monocytes decreased during ageing, and further decreased in AD but not in PD patients. Among the Aβ uptake-related receptors and enzymes, the expression of Toll‑like receptor 2 (TLR2) was reduced in monocytes from AD patients. Conclusions: 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 clearance function by blood monocytes represents a potential therapeutic strategy for AD.