Involvement of cerebrovascular semicarbazide-sensitive amine oxidase in the pathogenesis of Alzheimer's disease and vascular dementia.

Fibrillary tangles and senile plaques resulting from advanced aggregation of beta-amyloid and other proteins are pathological characteristics of Alzheimer's disease (AD). Cerebral amyloid angiopathy is quite common in AD. In fact, amyloid fibrils fuse to and emanate from the vascular basement membrane. Semicarbazide-sensitive amine oxidase (SSAO), located in outer membranes of vascular smooth muscles and endothelia, catalyzes deamination of methylamine-producing formaldehyde and hydrogen peroxide. SSAO is also involved in lymphocyte adhesion and is up-regulated in response to inflammation. SSAO-mediated generation of formaldehyde can induce protein (i.e. beta-amyloid) cross-linkage, deposition and subsequently plaque formation in the compartment adjacent to the cerebrovessels. Formaldehyde may cause cytotoxicity, which induces inflammation and release of more SSAO, producing a cascade of toxic cycle. Increased SSAO-mediated reaction may be chronically involved in the pathogenesis of vascular dementia and AD. Copyright 2001 Harcourt Publishers Ltd.