TY - JOUR
T1 - βPP and tau interaction
T2 - A possible link between amyloid and neurofibrillary tangles in Alzheimer's disease
AU - Giaccone, Giorgio
AU - Pedrotti, Barbara
AU - Migheli, Antonio
AU - Verga, Laura
AU - Perez, Jorge
AU - Racagni, Giorgio
AU - Smith, Mark A.
AU - Perry, George
AU - De Gioia, Luca
AU - Selvaggini, Carlo
AU - Salmona, Mario
AU - Ghiso, Jorge
AU - Frangione, Blas
AU - Islam, Khalid
AU - Bugiani, Orso
AU - Tagliavini, Fabrizio
PY - 1996/1
Y1 - 1996/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8546229
AN - SCOPUS:9044251598
VL - 148
SP - 79
EP - 87
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 1
ER -