Alpha 1-antichymotrypsin is present together with the beta-protein in monkey brain amyloid deposits.
The recent finding that the serine protease inhibitor, alpha 1-antichymotrypsin, is tightly associated with the amyloid deposits in brains of normal aged individuals and patients with Alzheimer's disease [Abraham C. R., Selkoe D. J. and Potter H. (1988) Cell 52, 487-501], suggests a role for this inhibitor in the progressive deposition of brain amyloid in humans. We have used immunocytochemistry to detect alpha 1-antichymotrypsin in the amyloid that accumulates in brains of aged monkeys, a naturally occurring animal model of Alzheimer-like neuropathology. In monkeys of increasing age, the earliest alpha 1-antichymotrypsin immunoreactivity was found in cortical perivascular cells, before the appearance of either Thioflavin S-detectable amyloid deposits or beta-protein reactivity in the vessel walls. Subsequently, amyloid deposits appeared in small meningeal blood vessels and cortical neuritic plaques. The oldest monkeys also showed microvascular amyloid in the cortical gray matter. Amyloid was never seen in white matter. The amyloid deposits in meningeal vessels were always positive for both beta-protein and alpha 1-antichymotrypsin, whereas in the cortex, alpha 1-antichymotrypsin immunoreactivity seemed to appear somewhat later than that of beta-protein. These findings demonstrate that two of the brain amyloid components of human senescence and Alzheimer's disease--the beta-protein and the protease inhibitor alpha 1-antichymotrypsin--are also present in the amyloid deposits of normal aged monkey brain. The extended molecular parallels between normal brain aging and Alzheimer's disease suggest that similar biochemical mechanisms may underlie progressive amyloid deposition in both situations.
Abraham
C R
CR
Department of Neurobiology, Harvard Medical School, Boston, MA.
Selkoe
D J
DJ
Potter
H
H
Price
D L
DL
Cork
L C
LC
D000375:Aging / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008253:Macaca mulatta; D015842:Serine Proteinase Inhibitors / Q000378:metabolism*; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D015842:Serine Proteinase Inhibitors; D000514:alpha 1-Antichymotrypsin