The role and therapeutic potential of monocytic cells in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a dementing neurodegenerative disorder without a cure. The abnormal parenchymal accumulation of beta-amyloid (Abeta) is associated with inflammatory reactions involving microglia and astrocytes. Increased levels of Abeta and Abeta deposition in the brain are thought to cause neuronal dysfunction and underlie dementia. Microglia, the brain resident cells of monocytic origin, have a potential ability to phagocytose Abeta but they also react to Abeta by increased production of proinflammatory toxic agents. Microglia originate from hemangioblastic mesoderm during early embryonic stages and from bone marrow (BM)-derived monocytic cells that home the brain throughout the neonatal stage of development. Recent studies indicate that BM or blood-derived monocytes are recruited to the diseased AD brain, associate with the Abeta depositions, and are more efficient phagocytes of Abeta compared with resident microglia. The clearance of Abeta deposition by these cells has been recently under intensive investigation and can occur through several different mechanisms. Importantly, peripheral monocytic cells of patients with AD appear to be deficient in clearing Abeta. This review will summarize the findings on the role of blood-derived cells in AD and discuss their therapeutic potential for treating patients suffering from this devastating disease.