Given the clinical features of AD, the severe atrophy of cerebral cortex that accompanies the disease, and the predominant cortical location of plaques and tangles, it is not surprising to find the most consistent changes in neuropeptides in this disease occurring in the cerebral cortex. The neuropeptide changes that have been reproducibly demonstrated in AD are reduced hippocampal and neocortical SS and CRF concentrations and a reduced CSF level of SS. In cerebral cortex, SS and CRF are found in GABAergic local circuit neurons in layers II, III, and VI. The function of these neurons is not well established, although these cells may act to integrate the flow of incoming and outgoing information in cerebral cortex. If this is true, then dysfunction of this integration could produce widespread failure of cerebrocortical function, resulting in the various neurobehavioral deficits seen in AD. The interpretation of neuropeptide changes in subcortical brain regions, either those that project to cortex, or those that are the efferent targets of cortical projections, is also uncertain. The observed neuropeptide abnormalities in these brain regions in AD are less consistent than are those seen in cerebral cortex. Perhaps the most intriguing result in these regions is the increases in galanin-immunoreactive terminals seen in the nucleus basalis of AD brains. Galanin has been shown to inhibit acetylcholine release and to impair memory function in rats (46,113).(ABSTRACT TRUNCATED AT 250 WORDS)