Chromogranin peptides in Alzheimer's disease.

Abstract

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 beta-amyloid plaques co-labelled with chromogranin A, 20% with secretoneurin and 15% with chromogranin B. Less than 5% of beta-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.

• Authors: Theresa Lechner, Christine Adlassnig, Christian Humpel, Walter A Kaufmann, Hans Maier, Karin Reinstadler-Kramer, Josef Hinterhölzl, Sushil K Mahata, Kurt A Jellinger, Josef Marksteiner
• Journal: Experimental gerontology (Exp Gerontol) Vol. 39 Issue 1 Pg. 101-13 (Jan 2004) ISSN: 0531-5565 [Print] England
• PMID: 14724070 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Calbindins
• Chromogranin A
• Chromogranins
• Glial Fibrillary Acidic Protein
• Neuropeptides
• S100 Calcium Binding Protein G
• Secretogranin II
• Synaptophysin
• secretoneurin

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (metabolism, pathology)
• Analysis of Variance
• Biomarkers (analysis)
• Brain Chemistry
• Calbindins
• Case-Control Studies
• Chromogranin A
• Chromogranins (analysis)
• Exocytosis (physiology)
• Female
• Glial Fibrillary Acidic Protein (analysis)
• Humans
• Immunohistochemistry (methods)
• Male
• Microglia (pathology)
• Neuropeptides (analysis)
• S100 Calcium Binding Protein G (analysis)
• Secretogranin II
• Synapses (pathology)
• Synaptophysin (analysis)