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Tau protein directly interacts with the amyloid β-protein precursor: Implications for Alzheimer's disease

Nature Medicine volume 1, pages 365–369 (1995)Cite this article

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, τ (tau) and amyloid β-protein, respectively, are well characterized, the molecular mechanisms responsible for their deposition in lesions are unknown. We demonstrate, using four independent techniques, that τ directly interacts with a conformation-dependent domain of the amyloid β-protein precursor (βPP) encompassing residues βPP714–723. The putative τ–binding domain includes βPP717 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.

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Authors and Affiliations

  1. Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio, 44106, USA

    M.A. Smith, S.L. Siedlak, P.L. Richey, P. Mulvihill, D. Praprotnik, R.N. Kalaria & G. Perry

  2. Department of Pathology, New York University Medical Center, New York, New York, 10016, USA

    J. Ghiso & B. Frangione

  3. Division of Neuropathology, Istituto Nazionale Neurologico Carlo Besta, 20133, Milan, Italy

    F. Tagliavini, G. Giaccone & O. Bugiani

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  1. M.A. Smith
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Smith, M., Siedlak, S., Richey, P. et al. Tau protein directly interacts with the amyloid β-protein precursor: Implications for Alzheimer's disease. Nat Med 1, 365–369 (1995). https://doi.org/10.1038/nm0495-365

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