Altered structural proteins in plaques and tangles: what do they tell us about the biology of Alzheimer's disease?
The progressive dysfunction and loss of neurons in Alzheimer's disease (AD) is accompanied by marked structural changes in innumerable neuronal cell bodies and neurites, particularly in limbic and association cortices. Qualitatively indistinguishable neuronal lesions occur in much smaller numbers during normal aging. Highly insoluble paired helical filaments (PHF) and antigenically related straight filaments accumulate in perikaryal tangles and the neurites of neuritic plaques. In addition, PHF antibodies reveal the presence of PHF antigens in many individual cortical neurites not clustered into discrete plaques. Recent studies in several laboratories indicate that altered forms of the microtubule-associated phosphoprotein, tau, are important constituents of PHF. Other neuronal cytoskeletal proteins, particularly microtubule-associated protein 2 and neurofilament, have also been associated with PHF. In contrast, the extracellular amyloid filaments found in the centers of many neuritic plaques and in cortical and meningeal vessels appear to be composed of hydrophobic low molecular weight protein(s) distinct from PHF. A major question for further study regards the cellular origin and role of microvascular amyloid in the degeneration of neurites of multiple neurotransmitter specificities in AD cortex. The widespread neuritic and perikaryal alterations in brain tissue are likely to represent, at least in part, the morphological substrate of cortical dysfunction in AD.
D000368:Aged; D000375:Aging / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009454:Neurofibrils / Q000378:metabolism / Q000473:pathology*; D016900:Neurofilament Proteins
D000682:Amyloid; D007381:Intermediate Filament Proteins; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins