Macrophages in Alzheimer’s disease: the blood-borne identity

• Published in: Journal of Neural Transmission 2010-08, Vol.117 (8), p.961-970
• Main Authors: Gate, David, Rezai-Zadeh, Kavon, Jodry, Dominique, Rentsendorj, Altan, Town, Terrence
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - pathology; Alzheimer's disease; Animals; Basic Neurosciences; Basic Neurosciences, Genetics and Immunology - Review; Blood-Brain Barrier - physiopathology; Brain - pathology; Genetics and Immunology - Review Article; Humans; Macrophages - physiology; Medicine; Medicine & Public Health; Models, Biological; Neurology; Neurosciences; Psychiatry
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-010-0422-7

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder clinically characterized by cognitive decline involving loss of memory, reasoning and linguistic ability. The amyloid cascade hypothesis holds that mismetabolism and aggregation of neurotoxic amyloid-β (Aβ) peptides, which are deposited as amyloid plaques, are the central etiological events in AD. Recent evidence from AD mouse models suggests that blood-borne mononuclear phagocytes are capable of infiltrating the brain and restricting β-amyloid plaques, thereby limiting disease progression. These observations raise at least three key questions: (1) what is the cell of origin for macrophages in the AD brain, (2) do blood-borne macrophages impact the pathophysiology of AD and (3) could these enigmatic cells be therapeutically targeted to curb cerebral amyloidosis and thereby slow disease progression? This review begins with a historical perspective of peripheral mononuclear phagocytes in AD, and moves on to critically consider the controversy surrounding their identity as distinct from brain-resident microglia and their potential impact on AD pathology.