Antioxidant protection and neurodegenerative disease: The role of amyloid-β and tau

Rudy J. Castellani*, Hyoung Gon Lee, George Perry, Mark A. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

In Alzheimer's disease (AD), the major components of senile plaques and neurofibrillary tangles, amyloid-β 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-β 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-β 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.

Original languageEnglish (US)
Pages (from-to)126-130
Number of pages5
JournalAmerican Journal of Alzheimer's Disease and Other Dementias
Volume21
Issue number2
DOIs
StatePublished - 2006
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Antioxidant
  • Free radical
  • Phosphorylation
  • Redox-active metals
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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