Amyloid‐β and monocytes in Alzheimer’s disease

Abstract

AbstractBackgroundCompelling evidence suggests that failure of Aβ clearance is a major mechanism of late‐onset Alzheimer’s disease (LOAD). The molecular basis remains unclear, but genome‐wide association studies (GWAS) strongly point to altered phagocytosis/endocytosis in the CNS and peripheral. Previously, we have demonstrated perturbation of monocyte basal and stimulated innate phagocytosis in LOAD.MethodFlow cytometry immunophenotyping (FCIP) is used to investigate the relationship between peripheral blood leukocyte transport Aβ and disease stage in AD patients.ResultsIn this study, we identified a subset of circulating intermediate monocytes (CD14+CD16+) that carry high amounts of Aβ dimers and co‐express the cell migration receptors CX3CR1 and CCR2. We then performed a quantitative study involving 165 AIBL participants and found that the number of monocytes carrying Aβ was decreased by 26% in AD and was inversely correlated with the subjects’ brain Aβ load and accumulation rate. Curiously, our further investigations revealed that the predominant type of infiltrating monocytes in human CSF are intermediate monocytes (CD45+CD14+CD16+).ConclusionThe passage of those cells across blood‐brain barrier and their physiological significance are unknown. But it suggests a possible mechanism for the transport of brain Aβ to the periphery by monocytes.