Macrophages in Alzheimer's disease: the blood-borne identity.
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-beta (Abeta) 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 beta-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.
Department of Biomedical Sciences, Regenerative Medicine Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Steven Spielberg Building, Room 361, Los Angeles, CA 90048, USA.
David
D
Gate
Kavon
K
Rezai-Zadeh
Dominique
D
Jodry
Altan
A
Rentsendorj
Terrence
T
Town
D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001921:Brain / Q000473:pathology*; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D008954:Models, Biological