2USDA-Human Nutrition Research Center on Aging
at Tufts University
Boston, Massachusetts 02111
Amyloid-beta and tau, the major components of senile plaques and
neurofibrillary tangles, respectively, have historically been
considered central mediators of the pathogenesis of Alzheimer disease.
However, efforts to understand disease mechanisms through understanding
either the processes involved in amyloid-beta deposition as senile plaques
or on the phosphorylation and aggregation of tau as neurofibrillary
tangles may be inappropriate. In fact, rather than initiators of
disease pathogenesis, both lesions occur consequent to oxidative stress
as relatively later events in neuronal pathogenesis. Moreover, there is
increasing evidence that the lesions function as a primary line of
antioxidant defense in both the aged and diseased brain. 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.
Key words:
Alzheimer disease, amyloid-beta, antioxidant, phosphorylation, tau
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