- The neuropeptides cholecystokinin (CCK) and somatostatin are synthesized in separate, but morphologically similar, populations of locally projecting neurons in cerebral cortex. Concentrations of somatostatin are markedly diminished in Alzheimer's disease (AD), suggesting possible dysfunction of the intrinsic cortical neurons in which it is produced. We determined whether cortical levels of CCK might be similarly affected in AD by dissecting postmortem brain samples from 14 histologically confirmed cases of AD and 17 age-matched controls and measuring CCK and somatostatin by radioimmunoassay. CCK-like immunoreactivity was significantly reduced in the AD brains by 24 to 38% in five of the 11 cortical areas examined but was normal in the remaining regions. Somatostatin concentrations measured in the same tissue extracts were consistently decreased by 45 to 65%. These results indicate that (1) CCK-immunoreactive neurons in cortex are affected by the AD process, and (2) the changes in levels of CCK are less dramatic than the reductions of somatostatin immunoreactivity.