βPP and tau interaction: A possible link between amyloid and neurofibrillary tangles in Alzheimer's disease

Giorgio Giaccone, Barbara Pedrotti, Antonio Migheli, Laura Verga, Jorge Perez, Giorgio Racagni, Mark A. Smith, George Perry, Luca De Gioia, Carlo Selvaggini, Mario Salmona, Jorge Ghiso, Blas Frangione, Khalid Islam, Orso Bugiani, Fabrizio Tagliavini

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Abstract

Extracellular deposition of amyloid fibrils and intraneuronal accumulation of paired helical filaments (PHFs) are the neuropathological hallmarks of Alzheimer's disease. The major constituent of amyloid fibrils is a 39- to 43- residue peptide (termed Aβ), which is derived from a 695- to 770-amino-acid precursor protein (termed βPP). The main component of PHFs identified so far is the microtubule-associated protein tau. Yet, there is no direct evidence of interconnection between these two pathological states. We report here that antibodies to an epitope located between residues 713 and 723 of βPP770 (ie, the transmembrane region of βPP distal to Aβ) consistently labeled PHFs in the brain of Alzheimer patients. Solid phase immunoassay showed that a peptide homologous to residues 713 to 730 of βPP770 bound tau proteins. This βPP peptide spontaneously formed fibrils in vitro and, in the presence of tau, generated dense fibrillary assemblies containing both molecules. These data suggest that βPP or βPP fragments containing the tau binding site are involved in the pathogenesis of PHFs in Alzheimer's disease.

Original languageEnglish
Pages (from-to)79-87
Number of pages9
JournalAmerican Journal of Pathology
Volume148
Issue number1
Publication statusPublished - Jan 1996

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Giaccone, G., Pedrotti, B., Migheli, A., Verga, L., Perez, J., Racagni, G., Smith, M. A., Perry, G., De Gioia, L., Selvaggini, C., Salmona, M., Ghiso, J., Frangione, B., Islam, K., Bugiani, O., & Tagliavini, F. (1996). βPP and tau interaction: A possible link between amyloid and neurofibrillary tangles in Alzheimer's disease. American Journal of Pathology, 148(1), 79-87.