INVOLVEMENT OF FREE OXYGEN RADICALS IN BETA-AMYLOIDOSIS - AN HYPOTHESIS

Compelling evidence suggests that cerebral deposition of aggregating b eta-amyloid protein may trigger the neurodegenerative cascades of Alzh eimer's disease, Down syndrome, and, to a lesser degree, normal aging. We propose further that free oxygen radicals are critically involved in beta-amyloidosis. Apart from the established role of free radicals in other amyloidoses, our proposal is consistent with a large number o f findings. Among these are (a) the salient relationship of Alzheimer' s disease with aging and the increase in free oxygen radical liberatio n with advancing age; (b) biochemical and analytic epidemiologic evide nce that free radical formation is increased in the disorder; (c) prel iminary evidence that quenching free radicals slows the clinical progr ession of Alzheimer's disease; (d) the early and invariable beta-amylo id accumulation in trisomy 21, a syndrome associated with elevated fre e radical activity and with concomitant high levels of beta-amyloid pr ecursor protein; (e) other factors that may be associated with increas ed liberation of free oxygen radicals and deposition of beta-amyloid p rotein. Possible mechanisms by which free radicals might modulate beta -amyloidosis are discussed.