Structural Proteins in Alzheimer’s Disease

Abstract

Neuritic (senile) plaques and neurofibrillary tangles (NFT) represent the principal structural alterations of neurons in presenile and senile dementia of the Alzheimer type (Alzheimer’s disease, AD). These two types of lesions are also found in much smaller numbers and in restricted topographical distribution in the brains of many neurologically normal individuals after the seventh decade. Tangles, plaques, and other structural changes found in Alzheimer brain tissue (granulovacuolar degeneration of neurons, amyloid angiopathy of small cerebral vessels, lipofuscin (LF) deposition in neurons and glia) are, therefore, qualitatively indistinguishable from the lesion that accompany normal brain aging, but are quantitatively much increased in AD. Neurofibrillary tangles are large, non-membrane-bound cytoplasmic masses of abnormal fibers found within the perikarya of neurons in hippocampus, amygdala, cerebral cortex, and certain deep gray nuclear structures. Numerous electron microscopic (EM) studies have concluded that the vast majority of fibers in these tangles have the appearance of tightly adherent pairs of helically wound, intermediate filaments, referred to as paired helical filaments (PHF) and having a maximum width of about 20 nm and a periodicity of roughly 80 nm [1–3]. It is also known that at least some of the abnormal neurites (dendrites and axonal terminals) making up the periphery of the senile plaque contain PHF [4]. Recently, a few laboratories have reported that bundles of straight (nonhelical) filaments of approximately 15nm width may also be found in neurons in Alzheimer cortex and may coexist within perikarya containing PHF [5–8].