Chromogranin peptides in Alzheimer's disease
Synaptic disturbances may play a key role in the pathophysiology of Alzheimer's disease. To characterize differential synaptic alterations in the brains of Alzheimer patients, chromogranin A, chromogranin B and secretoneurin were applied as soluble constituents for large dense core vesicles, sy...
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Published in | Experimental gerontology Vol. 39; no. 1; pp. 101 - 113 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Inc
2004
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Subjects | |
Online Access | Get full text |
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Summary: | Synaptic disturbances may play a key role in the pathophysiology of Alzheimer's disease.
To characterize differential synaptic alterations in the brains of Alzheimer patients, chromogranin A, chromogranin B and secretoneurin were applied as soluble constituents for large dense core vesicles, synaptophysin as a vesicle membrane marker and calbindin as a cytosolic protein.
In controls, chromogranin B and secretogranin are largely co-contained in interneurons, whereas chromogranin A is mostly found in pyramidal neurons. In Alzheimer's disease, about 30% of β-amyloid plaques co-labelled with chromogranin A, 20% with secretoneurin and 15% with chromogranin B. Less than 5% of β-amyloid plaques contained synaptophysin or calbindin, respectively. Semiquantitative immunohistochemistry revealed a significant loss for chromogranin B- and secretoneurin-like immunoreactivity in the dorsolateral, the entorhinal, and orbitofrontal cortex. Chromogranin A displayed more complex changes. It was the only chromogranin peptide to be expressed in glial fibrillary acidic protein containing cells. About 40% of chromogranin A immunopositive plaques and extracellular deposits were surrounded and pervaded by activated microglia.
The present study demonstrates a loss of presynaptic proteins involved in distinct steps of exocytosis. An imbalanced availability of chromogranins may be responsible for impaired neurotransmission and a reduced functioning of dense core vesicles. Chromogranin A is likely to be a mediator between neuronal, glial and inflammatory mechanisms found in Alzheimer disease. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0531-5565 1873-6815 |
DOI: | 10.1016/j.exger.2003.09.018 |