The organization of the microtubule associated protein tau in Alzheimer paired helical filaments

Abstract

Neurofibrillary tangles (NFT) of paired helical filaments (PHF) are the most characteristic brain lesions of Alzheimer disease and their abundance determines the diagnosis. This histopathological hallmark occurs with greater frequency in patients with clinical dementia of the Alzheimer type than in normal individuals of the same age. Therefore, it is important that we establish and understand the arrangement of subunits in PHF. This knowledge, we believe, could be key to understanding the pathogenesis of neurofibrillary degeneration.Intracellular Alzheimer NFT fixed in OsO4or KMnO4in the absence of glutaraldehyde treatment were first observed by transmission electron microscopy (TEM) of thin sections and reported by Kidd. The tangles he observed contained helical pairs of ~10 nm filaments separated center to center by 15 nm with a double helical period of ~160 nm that he named paired helical filaments. Subsequent thin sectioning work with a similar fixation treatment confirmed that the PHF were helical with crossover width, T=12.8±2 nm, and a wide region, W=24±3.1 nm, which occured every L=65−80 nm.