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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, R.ab3a 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.
Key Words: Alzheimer disease; Rab3a; SNAP-25; Synapsin; Synaptophysin; Synaptotagmin; Syntaxin.
INTRODUCTION
Senile (diffuse and neuritic) plaques, neurofibrillary tangles, and loss of neurons and synapses represent the most characteristic pathological findings in the brain of patients with Alzheimer disease.
Dystrophic neurites surrounding amyloid deposits are major components of neuritic plaques in normal aging and in patients with Alzheimer disease (1). Dystrophic neurites, most of them presynaptic axonal terminals, contain degenerating mitochondria, dense bodies, and paired helical filaments (2-4). Immunohistochemical studies have also shown the presence of different neuropeptides in dystrophic neurites in patients with Alzheimer disease, thus suggesting a convergence of different neuronal populations in senile plaques (5-8). In addition to dystrophic neurites, early studies with the Golgi method showed aberrant neuronal sprouting in the vicinity of amyloid deposits in the cerebral neocortex and hippocampus (9-14). Recent studies have corroborated this observation by demonstrating the presence of GAP-43, a protein involved in neuronal development and plasticity (15), in aberrant sprouting associated with senile plaques (16). A major concern in relation to neurotransmitter release and synaptic pathology associated with senile plaques has prompted the study of specific markers in the brains of patients with Alzheimer disease. Chromogranin A, a component of dense-core vesicles, is strongly expressed in large aberrant neurites surrounding amyloid deposits (17-19), whereas synaptophysin, a synaptic vesicle membrane protein linked with...