Chromogranin peptides in Alzheimer's disease

• Published in: Experimental gerontology Vol. 39; no. 1; pp. 101 - 113
• Main Authors: Lechner, Theresa, Adlassnig, Christine, Humpel, Christian, Kaufmann, Walter A, Maier, Hans, Reinstadler-Kramer, Karin, Hinterhölzl, Josef, Mahata, Sushil K, Jellinger, Kurt A, Marksteiner, Josef
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 2004
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Analysis of Variance; Biomarkers - analysis; Brain Chemistry; Calbindins; Case-Control Studies; Chromogranin A; Chromogranin B; Chromogranins - analysis; Exocytosis - physiology; Female; Glial Fibrillary Acidic Protein - analysis; Human brain; Humans; Immunohistochemistry - methods; Male; Microglia - pathology; Neuropeptides - analysis; S100 Calcium Binding Protein G - analysis; Secretogranin II; Synapses - pathology; Synaptophysin - analysis; Human brain; Chromogranin B; Chromogranin A; Alzheimer's disease
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2003.09.018

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.