Development of senile plaques. Relationships of neuronal abnormalities and amyloid deposits.
The evolution of senile plaques and the relationships among neuritic elements, extracellular deposits of the beta-amyloid protein (beta/A4), and vascular beta/A4 are poorly understood. Immunocytochemical methods were used to examine fixed-frozen prefrontal cortices of 14 rhesus monkeys (Macaca mulatta) (14 to 37 years of age) for the presence of abnormal fibers/neurites, alpha 1-antichymotrypsin (alpha-ACT), and beta/A4. Age-associated alterations included abnormal fibers/neurites, presence of beta/A4, and association of alpha-ACT with beta/A4 in plaques and blood vessels. Vascular amyloid was present only in the oldest monkeys. The topographic distribution of abnormal fibers/neurites was mapped with acetylcholinesterase (AChE) histochemistry, and deposits of amyloid were visualized with immunocytochemistry for beta/A4. beta/A4 often was associated with neurites, but many neurites lacked demonstrable beta/A4. Thus in aged monkeys, abnormal neurites may provide one type of focus for the accumulation of the amyloid precursor, which is subsequently abnormally processed to form beta/A4. Our data in rhesus monkeys suggest that fiber and neuritic abnormalities increase with age and that they may precede the majority of beta/A4 deposits; the initial stages of neurite formation and parenchymal amyloid deposits may be independent of the appearance of vascular amyloid; and these processes may be synergistic with advanced age.
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Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2181.
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Beyreuther
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D000110:Acetylcholinesterase / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008253:Macaca mulatta; D008875:Middle Aged; D009454:Neurofibrils / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D013194:Staining and Labeling; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism
D000682:Amyloid; D000514:alpha 1-Antichymotrypsin; D000110:Acetylcholinesterase