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

The processes involved with beta -amyloid (A beta) degradation and clearance in human brain are not well understood. We hypothesized that the distribution 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 upon plaque counts, oxidized A beta was present within 46-48% of diffuse and primitive plaques and 98% of cored plaques. Dense punctate deposits of oxidized A beta were distributed throughout the neuropil in AD and DS brains but were also present within controls with mild neuropathology and isolated cognitive impairments. Confocal studies indicate that punctate oxidized A beta deposits were within activated microglia. Oxidatively modified A beta may reflect the efforts of microglial cells to take up and degrade A beta. Oxidative modification of A beta may be an early event in A beta pathogenesis and may be important for plaque biogenesis. (C) 2001 Academic Press.