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, 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.
Lechner
Theresa
T
Department of Psychiatry, Anichstrasse 35, Innsbruck A-6020, Austria.
Adlassnig
Christine
C
Humpel
Christian
C
Kaufmann
Walter A
WA
Maier
Hans
H
Reinstadler-Kramer
Karin
K
Hinterhölzl
Josef
J
Mahata
Sushil K
SK
Jellinger
Kurt A
KA
Marksteiner
Josef
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D001923:Brain Chemistry; D064026:Calbindins; D016022:Case-Control Studies; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis*; D005089:Exocytosis / Q000502:physiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D017628:Microglia / Q000473:pathology; D009479:Neuropeptides / Q000032:analysis; D064030:S100 Calcium Binding Protein G / Q000032:analysis; D053381:Secretogranin II; D013569:Synapses / Q000473:pathology; D016708:Synaptophysin / Q000032:analysis
D015415:Biomarkers; D064026:Calbindins; D053379:Chromogranin A; D002864:Chromogranins; D005904:Glial Fibrillary Acidic Protein; D009479:Neuropeptides; D064030:S100 Calcium Binding Protein G; D053381:Secretogranin II; D016708:Synaptophysin; C081159:secretoneurin