title: Tau protein directly interacts with the amyloid beta-protein precursor: implications for Alzheimer's disease.
abstract: The simultaneous presence of intracellular neurofibrillary tangles (NFT) and extracellular senile plaques in Alzheimer's disease (AD) suggests that the two lesions could be synergistically interrelated. However, although the main protein components of NFT and senile plaques, tau (tau) and amyloid beta-protein, respectively, are well characterized, the molecular mechanisms responsible for their deposition in lesions are unknown. We demonstrate, using four independent techniques, that tau directly interacts with a conformation-dependent domain of the amyloid beta-protein precursor (beta PP) encompassing residues beta PP714-723. The putative tau-binding domain includes beta PP717 mutation sites that are associated with familial forms of AD. Our findings strongly suggest that NFT and senile plaques, often thought of as independent structures, may play a role in each other's formation during the pathogenesis of AD.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
authors.forename: S L
authors.initials: SL
authors.lastname: Siedlak
authors.forename: P L
authors.initials: PL
authors.lastname: Richey
authors.forename: P
authors.initials: P
authors.lastname: Mulvihill
authors.forename: J
authors.initials: J
authors.lastname: Ghiso
authors.forename: B
authors.initials: B
authors.lastname: Frangione
authors.forename: F
authors.initials: F
authors.lastname: Tagliavini
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
authors.forename: O
authors.initials: O
authors.lastname: Bugiani
authors.forename: D
authors.initials: D
authors.lastname: Praprotnik
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D016875:tau Proteins