Regional Neuropeptide Pathology in Alzheimer's Disease: Corticotropin-Releasing Factor and Somatostatin

Abstract

Background: the neuropeptides most consistently reported to be altered in Alzheimer’s disease are corticotropin-releasing factor and somatostatin (somatotropin-release inhibiting factor), although this has been previously assessed in a limited number of brain regions. Methods: in order to comprehensively characterize the involvement of these two anatomically distinct neuropeptide systems in Alzheimer’s disease and to determine if they are equally involved in the associated pathology, we measured the concentration of corticotropin-releasing factor and somatostatin in post-mortem brain tissue. Radioimmunoassay of 24 cortical and 13 sub-cortical brain regions from 16 cases of neuropathologically confirmed AD and 9 non-Alzheimer’s disease controls were performed and significant differences in group regional neuropeptide concentrations were sought using the Student Newman-Keuls test after ANOVA. Results: comparison of group mean regional neuropeptide concentrations revealed several brain regions where both peptides were decreased in Alzheimer’s disease and some regions where only one of the two peptides were decreased, while still other regions exhibited no changes in either peptide. These changes were principally found in frontal and temporal cortex, with few subcortical regions exhibiting pathologic changes in peptide concentration. Regional peptide content was correlated among peptides and with duration of dementia in several brain regions. Conclusions: these data support the hypothesis that the somatostatin- and corticotropin-releasing factor containing neurons are pathologically involved in AD and that the involved neurons are limited to specific areas of the brain.