Synaptic proteins in Alzheimer's disease.
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 B, 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 gyyrs, the CA1 area, the subiculum and in layers I, III and V of the entorhinal cortex. The present study demonstrates that chromogranin peptides are markers for human hippocampal pathways. Thee 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.
Marksteiner
Josef
J
Institute for Biochemical Pharmacology, Department of Psychiatry, University Innsbruck, Austria. j.marksteiner@uibk.ac.at
Kaufmann
Walter A
WA
Gurka
Peter
P
Humpel
Christian
C
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D053381:Secretogranin II; D022142:Secretory Vesicles / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D053379:Chromogranin A; D053378:Chromogranin B; D002864:Chromogranins; D009479:Neuropeptides; C109924:PE 11 peptide; D010446:Peptide Fragments; D011506:Proteins; D053381:Secretogranin II; C081159:secretoneurin