disease:The roleofamyloid-f3and tau

InAlzheimer sdisease (AD), themajor components of senile plaques andneurofibrillary tangles, amyloid-f3 andtau, respectively, arethought bymanytoplayakey roleindisease initiation andprogression. However, herein wepropose that rather thanbeing initiators of disease pathogenesis, thelesions that characterize AD, senile plaques andneurofibrillary pathology, occur consequent tooxidative stress and,importantly, function as aprimary line ofantioxidant defense. Importantly, this paradigm shift inthinking abouttherole oflesions in disease also provides anexplanation fortheappearance ofbothamyloid-/3 andtauincontrol individuals given theincreased levels ofoxidative stress associated with theagedbrain. InAD,oxidative stress isnotonly high butchronic andissuperimposed uponanage-related vulnerable environment. Therefore, onewould predict, successfully, anincreased lesion loadinpatients with AD aboveandbeyond that seeninnormal aging. The notion that amyloid-f3 andtauaccumulations indicate adaptation and,likely, physiological processes sheds light onthepathological expression ofdisease andcalls into question therationale ofcurrent therapeutic efforts targeted toward lesion removal.