| Alzheimer's disease (AD) tissue is characterized by two pathological structures; the neurofibrillary tangle (NFT), which is found in the somatodendritic compartment of the cell, and the neuritic plaque (NP), which is in the neuropil. Previous studies of the composition of AD pathology have focused on the cytoskeletal elements which are normally distributed in the somatodendritic compartment of the neuron. Very little attention has been given to the cytoskeletal elements, which are normally localized to the axon, and how they may play a role in AD pathology.; Our immunohistochemical and biochemical studies show that the microtubule-associated protein, tau, a form of which is normally concentrated in the axon, is a component of the paired helical filaments (PHFs) in the NFTs and peripheral neurites of the NP. Identical results in biopsy tissue preclude that the accumulation of tau in the cell body of affected neurons is a result of a postmortem artefact. In contrast to the tau in the axon, the pathology-associated tau in both biopsy and autopsy tissue appears to be modified by phosphorylation. The accumulation of tau in disease-affected neuronal cell bodies is not unique to AD, but occurs in the pathologies of several neurodegenerative diseases. AD-affected neurons may provide a model system for studying the mechanism(s) of cytoskeletal sorting. |
