Chapter 17 Neuronal cytoskeleton in aging and dementia

Abstract

This chapter discusses the morphology and the biochemistry of neurofibrillary changes and their analogs in animal models. One of the cellular and molecular changes with aging is the formation of argentophilic intracellular neurofibrillary tangles in selected neurons of the aged human brain. These extraordinary neurofibrillary changes are seen in great abundance in several adult and late life dementias, especially the Alzheimer disease/senile dementia of the Alzheimer type (AD/SDAT). The Alzheimer neurofibrillary tangles (ANT) are composed of paired helical filaments (PHF). Bundles of these PHF are also found in the dystrophic neurites of the neuritic (senile) plaque, the second leading histopathological lesion of AD/SDAT. The normal neurofibrils are microtubules, neurofilaments, and microfilaments. The microtubules of the neuron are apparently identical to those in glial cells and all eukaryotic cells. PHF have, by sodium dodecyl sulfate polyacrylamide gel electrophoresis, a heterogeneous polypeptide composition, which might vary from 2–3 major bands in the 45 kDa–62 kDa area to a ladder of polypeptides with molecular weight difference of less than 5 kDa between the adjacent bands. This protein composition of isolated PHF is different from that of neurofilaments, microtubules, plaque amyloid, and scrapie-associated fibrils. Although a number of normal brain polypeptides have been shown to cross-react immunochemically with PHF, only the presence of microtubule-associated proteins, tau, in PHF has been demonstrated.