Cortical and subcortical neuropeptides in Alzheimer's disease

Alexander P. Auchus, Robert C. Green, Charles B. Nemeroff

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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. Because the nucleus basalis is the principle source of cholinergic afferents to the cerebral cortex, and because acetylcholine has been repeatedly shown to be important in memory function, the presence of high levels of an inhibitory substance like galanin in this brain region suggests a possible role for galanin in the pathogenesis of AD. It remains unclear whether increased galanin in nucleus basalis is a primary change in AD or whether it represents an epiphenomenon secondary to the loss of cholinergic nucleus basalis neurons. In either case, development of pharmaceutical agents that could interact with the galanin system in the nucleus basalis may be a promising approach to the treatment of AD. As newer methods of analyzing prohormone mRNA and receptor mRNA expression are applied to AD, a better understanding of the involvement of neuropeptide-containing neurons in this disease will be obtained. This, coupled with the development of radioligands to label peptide receptors in vivo using position-emission tomography, will undoubtedly provide considerably more information concerning the pathophysiology of neuropeptidergic neurons in AD.

Original languageEnglish (US)
Pages (from-to)589-595
Number of pages7
JournalNeurobiology of aging
Volume15
Issue number4
DOIs
StatePublished - 1994
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

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