BETA-PP AND TAU INTERACTION - A POSSIBLE LINK BETWEEN AMYLOID AND NEUROFIBRILLARY TANGLES IN ALZHEIMERS-DISEASE

Extracellular deposition of amyloid fibrils and intraneuronal accumula tion of paired helical filaments (PHFs) are the neuropathological hall marks of Alzheimer's disease. The major constituent of amyloid fibrils is a 39- to 43-residue peptide (termed A beta), which is derived from a 695- to 770-amino-acid precursor protein (termed beta PP). The main component of PHFs identified so far is the microtubule-associated pro tein tau. Yet, there is no direct evidence of interconnection between these two pathological states. We report here that antibodies to an ep itope located between residues 713 and 723 of beta PP770 (ie, the tran smembrane region of beta PP distal to A beta) consistently labeled PHF s in the brain of Alzheimer patients. Solid phase immunoassay showed t hat a peptide homologous to residues 713 to 730 of beta PP770 bound ta u proteins. This beta PP peptide spontaneously formed fibrils in vitro and, in the presence of tau, generated dense fibrillary assemblies co ntaining both molecules. These data suggest that beta PP or beta PP fr agments containing the tau binding site are involved in the pathogenes is of PHFs in Alzheimer's disease.