Neuropathologic, neurochemical and immunocytochemical characteristics of aluminum-induced neurofilamentous degeneration.
Inoculation of aluminum salts or metallic aluminum into the central nervous system of rabbits produces an encephalomyelopathy accompanied by widespread neurofibrillary degeneration (NFD) affecting restricted neuronal populations. Some investigators have suggested that this preparation may serve as an animal model for human neurodegenerative disorders, such as Alzheimer's disease (AD), in which neurofibrillary tangle (NFT) formation is a prominent histopathologic finding. However, neurochemical, immunocytochemical and behavioral features of the model are largely unknown and its neuropathology only partially described. We have undertaken a series of experiments designed to further characterize these aspects of the model. We have used an intraventricular route of injection of aluminum chloride and found that the distribution of NFD in rabbit brain is similar to the distribution of NFT formation in AD. Immunocytochemical probes demonstrate that phosphorylated neurofilaments accumulate in neuronal perikarya containing NFD, and double labelling techniques suggest that NFD affects primarily projection type neurons. The neurochemical profile of aluminum intoxicated rabbits shows both similarities and discrepancies to that of AD. Finally, as reported in a companion article in this issue of Neurotoxicology (Solomon and Pendlebury, 1988), aluminum-exposed rabbits develop learning and memory deficits which are strongly correlated with the degree of whole brain NFD but not with motor, sensory or motivational factors. We conclude that aluminum-induced NFD may have relevance for understanding NFT formation in AD and other neurodegenerative disorders in which abnormalities of the neuronal cytoskeletal architecture are present.
Pendlebury
W W
WW
Department of Pathology, University of Vermont College of Medicine, Burlington.
Beal
M F
MF
Kowall
N W
NW
Solomon
P R
PR
D000535:Aluminum / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D003599:Cytoskeleton / Q000187:drug effects*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007382:Intermediate Filaments / Q000187:drug effects* / Q000473:pathology; D008854:Microscopy, Electron; D011817:Rabbits
D000535:Aluminum