title: Amyloid-beta and tau serve antioxidant functions in the aging and Alzheimer brain.
abstract: Historically, amyloid-beta and tau (tau), the major components of senile plaques and neurofibrillary tangles, respectively, have been considered central mediators of the pathogenesis of Alzheimer disease. Therefore, efforts to understand disease mechanisms have concentrated on understanding either the processes involved in amyloid-beta deposition as senile plaques or on the phosphorylation and aggregation of tau as neurofibrillary tangles. However, in light of recent evidence, such "lesion-centric" approaches look to be inappropriate. In fact, rather than initiators of disease pathogenesis, the lesions occur consequent to oxidative stress and function as a primary line of antioxidant defense. Given this, it is perhaps not surprising that the increased sensitivity to oxidative stress in the aged brain, even in control individuals, is invariably marked by the appearance of both amyloid-beta and tau. Additionally, in Alzheimer disease, where chronic oxidative stress persists and is superimposed upon an age-related vulnerable environment, one would predict, and there is, an increased lesion load. The notion that amyloid-beta and tau function as protective components brings into serious question the rationale of current therapeutic efforts targeted toward lesion removal.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. mas21@po.cwru.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Gemma
authors.initials: G
authors.lastname: Casadesus
authors.forename: James A
authors.initials: JA
authors.lastname: Joseph
authors.forename: George
authors.initials: G
authors.lastname: Perry
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000502:physiology*; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D006801:Humans; D016874:Neurofibrillary Tangles / Q000502:physiology*; D018384:Oxidative Stress; D010766:Phosphorylation; D016875:tau Proteins / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D016875:tau Proteins