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 β-amyloid protein (β/A4), and vascular β/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, α₁-antichymotrypsin (α-ACT), and β/A4. Age-associated alterations included abnormal fibers/neurites, presence of β/A4, and association of α-ACT with β/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 β/A4. β/A4 often was associated with neurites, but many neurites lacked demonstrable β/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 β/A4. Our data in rhesus monkeys suggest that fiber and neuritic abnormalities increase with age and that they may precede the majority of β/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.