Oxidation of a beta and plaque biogenesis in Alzheimer's disease and Down syndrome

The processes involved with beta -amyloid (A beta) degradation and clearanc e in human brain are not well understood. We hypothesized that the distribu tion of oxidatively modified A beta, as determined by an affinity-purified antibody in the entorhinal and frontal cortices of Alzheimer's disease (AD) , Down syndrome (DS), nondemented elderly control cases, and canine brain, would provide insight into the mechanisms of A beta accumulation. Based upo n plaque counts, oxidized A beta was present within 46-48% of diffuse and p rimitive plaques and 98% of cored plaques. Dense punctate deposits of oxidi zed A beta were distributed throughout the neuropil in AD and DS brains but were also present within controls with mild neuropathology and isolated co gnitive impairments. Confocal studies indicate that punctate oxidized A bet a deposits were within activated microglia. Oxidatively modified A beta may reflect the efforts of microglial cells to take up and degrade A beta. Oxi dative modification of A beta may be an early event in A beta pathogenesis and may be important for plaque biogenesis. (C) 2001 Academic Press.