title: Antioxidant protection and neurodegenerative disease: the role of amyloid-beta and tau.
abstract: In Alzheimer's disease (AD), the major components of senile plaques and neurofibrillary tangles, amyloid-beta and tau, respectively, are thought by many to play a key role in disease initiation and progression. However, herein we propose that rather than being initiators of disease pathogenesis, the lesions that characterize AD, senile plaques and neurofibrillary pathology, occur consequent to oxidative stress and, importantly, function as a primary line of antioxidant defense. Importantly, this paradigm shift in thinking about the role of lesions in disease also provides an explanation for the appearance of both amyloid-beta and tau in control individuals given the increased levels of oxidative stress associated with the aged brain. In AD, oxidative stress is not only high but chronic and is superimposed upon an age-related vulnerable environment. Therefore, one would predict, successfully, an increased lesion load in patients with AD above and beyond that seen in normal aging. The notion that amyloid-beta and tau accumulations indicate adaptation and, likely, physiological processes sheds light on the pathological expression of disease and calls into question the rationale of current therapeutic efforts targeted toward lesion removal.
authors.affiliation: Department of Pathology, University of Maryland, Baltimore, Maryland, USA.
authors.forename: Rudy J
authors.initials: RJ
authors.lastname: Castellani
authors.forename: Hyoung-Gon
authors.initials: HG
authors.lastname: Lee
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism; D018384:Oxidative Stress; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D016875:tau Proteins