Oxidation of Aβ and Plaque Biogenesis in Alzheimer's Disease and Down Syndrome

Neurobiology of Disease

William Garzon-Rodriguez¹  Julene K. Johnson²  Carl W. Cotman³  Ira T. Lott⁴  Charles Glabe⁵  Elizabeth Head⁵ 

[1] Dementia, University of California, Irvine, California, 92697-4540;Department of Molecular Biology and Biochemistry, University of California, Irvine, California, 92697-3900;Mental Retardation Center, Department of Pediatrics, University of California, Irvine, California, 92697;Universidad Nacional Autonoma de Mexico, Facultad de Quimica, 04510, Mexico, D.F. Mexico;;Institute for Brain Aging &

关键词: Alzheimer's disease;    amyloid;    brain aging;    canine;    Down syndrome;    microglia, oxidative damage;   

DOI  :  

来源: DOAJ

【 摘 要 】

The processes involved with β-amyloid (Aβ) degradation and clearance in human brain are not well understood. We hypothesized that the distribution of oxidatively modified Aβ, 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 Aβ accumulation. Based upon plaque counts, oxidized Aβ was present within 46–48% of diffuse and primitive plaques and 98% of cored plaques. Dense punctate deposits of oxidized Aβ 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 Aβ deposits were within activated microglia. Oxidatively modified Aβ may reflect the efforts of microglial cells to take up and degrade Aβ. Oxidative modification of Aβ may be an early event in Aβ pathogenesis and may be important for plaque biogenesis.

【 授权许可】

Unknown