Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease

Errol B. De Souza, Peter J. Whitehouse, Michael J. Kuhar, Donald L. Price, Wylie W. Vale

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer's disease is a progressive degenerative disease of the nervous system characterized neuropathologically by the presence of senile plaques and neurofibrillary tangles in amygdala, hippocampus and neocortex1-4. Dysfunction and death of basal forebrain cholinergic neurones projecting to forebrain targets5,6 are associated with marked decreases in cholinergic markers, including the activity of choline acetyltransferase (ChAT)2,3,7-9. Although cortical levels of somatostatin 10-12 and somatostatin receptors13 are reduced in Alzheimer's, no consistent changes have been reported in other neuropeptide systems12,14-17. We have now examined in control and Alzheimer's brain tissues pre- and postsynaptic markers of corticotropin-releasing factor (CRF), a hypothalamic peptide regulating pituitary-adrenocortical secretion 18,19 which also seems to act as a neu retransmitter in the central nervous system (CNS) (reviewed in refs 20, 21). We have found that in Alzheimer's, the concentrations of CRF-like immunoreactivity (CRF-IR) are reduced and that there are reciprocal increases in CRF receptor binding in affected cortical areas. These changes are significantly correlated with decrements in ChAT activity. Our results strongly support a neurotransmitter role for CRF in brain and demonstrate, for the first time, a modulation of CNS CRF receptors associated with altered CRF content. These observations further suggest a possible role for CRF in the pathophysiology of the dementia. Future therapies directed at increasing CRF levels in brain may prove useful for treatment.

Original languageEnglish (US)
Pages (from-to)593-595
Number of pages3
JournalNature
Volume319
Issue number6054
DOIs
StatePublished - Dec 1 1986

ASJC Scopus subject areas

  • General

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