TAU-PROTEIN DIRECTLY INTERACTS WITH THE AMYLOID BETA-PROTEIN PRECURSOR - IMPLICATIONS FOR ALZHEIMERS-DISEASE

The simultaneous presence of intracellular neurofibrillary tangles (NF T) and extracellular senile plaques in Alzheimer's disease (AD) sugges ts that the two lesions could be synergistically interrelated. However , although the main protein components of NFT and senile plaques, (tau ) and amyloid beta-protein, respectively, are well characterized, the molecular mechanisms responsible for their deposition in lesions are u nknown. We demonstrate, using four independent techniques, that tau di rectly interacts with a conformation-dependent domain of the amyloid b eta-protein precursor (beta PP) encompassing residues beta PP714-723. The putative tau-binding domain includes beta PP717 mutation sites tha t are associated with familial forms of AD. Our findings strongly sugg est that NFT and senile plaques, often thought of as independent struc tures, may play a role in each other's formation during the pathogenes is of AD.