4.4 Article

Synaptic proteins in Alzheimer's disease

期刊

JOURNAL OF MOLECULAR NEUROSCIENCE
卷 18, 期 1-2, 页码 53-63

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HUMANA PRESS INC
DOI: 10.1385/JMN:18:1-2:53

关键词

chromogranin A; chromogranin B; secretogranin II; immunocytochemistry; large dense core vesicles

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Chromogranin A, chromogranin B, and secretogranin II are acidic proteins which are stored in large dense core vesicles of neurons. An antiserum, raised against a synthetic peptide (PE-11), present in the chromogranin B molecule, and an antiserum raised against secretoneurin contained in the secretogranin II sequence, was used to localize these peptides together with chromogranin A in the human hippocampal formation. The distribution of these peptides was investigated in Alzheimer's disease and compared to control subjects. Chromogranin A, chromogranin 13, and secretogranin II are distinctly distributed with an overlap in their distribution patterns. They were only detected in neuronal structures. The highest density of immunoreactivity was found for chromogranin B. A layer specific distribution was especially obvious in the inner molecular layer of the dentate gyrus as secretoneurin-like immunoreactivity was restricted to its innermost part whereas that of chromogranin B was highly concentrated throughout the inner molecular layer. In Alzheimer's disease, about 10 to 20% of the amyloid-immunoreactive plaques contained either chromogranin A, chromogranin B or secretoneurin. The density of secretoneurin-and chromogranin B-like immunoreactivity was significantly reduced in the inner molecular layer of the dentate gyrus, the CA1 area, the subiculum and in layers II, III and V of the entorhinal cortex. The present study demonstrates that chromogranin peptides are markers for human hippocampal pathways. They are particularly suitable to study nerve fibers, terminating at the inner molecular layer of the dentate gyrus. Chromogranin peptides have a potential as neuronal markers for synaptic degeneration in Alzheimer's disease.

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