Alteration of neuritic cytoarchitecture in Alzheimer disease.
Individuals afflicted with Alzheimer disease (AD) demonstrate two prominent brain structural alterations: senile plaques and neurofibrillary tangles (NFT) (Selkoe, 1986). Not appreciated until recently is a third quantitatively significant structure, the dystrophic neurite. Many of these altered neurites are focally associated with amyloid deposits, and together they comprise the senile plaque. However, the great majority of the abnormal neurites in AD are independent of senile plaques (Braak, et al., 1986). Recent advances have yielded considerable information on the chemical nature of the extracellular amyloid (Kang, et al., 1987; Tanzi, et al., 1988) which comprises the central portion of the senile plaque, but there is much yet to be unraveled concerning both the nature of NFT and the relationship between senile plaques and NFT (Selkoe, 1987). While the NFT is principally comprised of 20 nm helically wound filaments, descriptively termed paired helical filaments (PHF) (Kidd, 1963; Wisniewski, et al., 1976) occasionally 12-15 nm straight filaments are also present (Perry, et al., 1987c). We have found that the predominant filaments in dystrophic neurites of AD are straight filaments which are morphologically indistinguishable from those found within NFT. The abnormal neuritic filaments and PHF share microtubule associated protein, tau, and ubiquitin immunoreactivity. The prevalence of altered neurites suggests that reorganization of neuritic cytoarchitecture in AD, as demonstrated by the formation of abnormal polymers structurally, and by inference functionally distinct from the normal cytoskeleton, may constitute a more important part of the cytopathological change of AD than previously appreciated.
Onorato
M
M
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106.
Mulvihill
P
P
Connolly
J
J
Galloway
P
P
Whitehouse
P
P
Perry
G
G
D000544:Alzheimer Disease / Q000473:pathology*; D000686:Amyloidosis / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology*; D003599:Cytoskeleton / Q000473:pathology*; D006801:Humans; D007382:Intermediate Filaments / Q000473:pathology*; D009454:Neurofibrils / Q000473:pathology*