The recent finding that the serine protease inhibitor, α1-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 α1-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 α1-antichymotrypsin immunoreactivity was found in cortical perivascular cells, before the appearance of either Thioflavin S-detectable amyloid deposits or β-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 β-protein and α1-antichymotrypsin, whereas in the cortex, α1-antichymotrypsin immunoreactivity seemed to appear somewhat later than that of β-protein. These findings demonstrate that two of the brain amyloid components of human senescence and Alzheimer's disease-the β-protein and the protease inhibitor α1-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.
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