Dystrophic neurites of senile plaques are defective in proteins involved in exocytosis and neurotransmission.

Abstract

Dystrophic neurites are major components of neuritic (both immature and mature) senile plaques in Alzheimer disease. Previous studies have shown strong immunoreactivity for different neuropeptides, and chromogranin A, a protein associated with dense-core vesicles, in dystrophic neurites. In the present study, antibodies to synaptophysin, synapsin, Rab3a and synaptotagmin (synaptic vesicle proteins), and SNAP-25 (synaptosomal-associated protein of 25 kD) and syntaxin (presynaptic plasma membrane proteins) have been used to learn about the dystrophic neurite equipment of proteins that are necessary for the docking and fusion of synaptic vesicles, and then for exocytosis and neurotransmission. The present results have shown that, although most neuritic senile plaques have chromogranin A- and SNAP-25-immunoreactive dystrophic neurites, only a percentage of them contain synaptophysin, and a minority contain synaptotagmin and Rab3a. Dystrophic neurites do not contain synapsin and syntaxin. These results show that dystrophic neurites of senile plaques are defective in proteins that control exocytosis and neurotransmission.