ABSTRACT
For nearly a century, the pathological hallmarks of Alzheimer’s disease (AD), namely senile plaques and neurofibrillary tangles (NFT), have been suspected to play a major role in disease pathogenesis. This, not surprisingly, has led the field to focus on the biochemistry of amyloid-b deposition as senile plaques, or the phosphorylation and aggregation of tau as NFT. In this review we take a contrary view, where, rather than remaining initiators of disease pathogenesis, we suspect that the lesions function as a primary line of antioxidant defense. If amyloid-b and tau accumulations reflect a physiological reaction to chronic stress, the rationale of current therapeutic efforts targeted toward lesion removal would obviously be misguided. Expanding beyond AD, we suspect that this concept of protection is also true for misfolded proteins and pathological lesions in other neurodegenerative diseases.
