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

Nature volume 319, pages 593–595 (1986)Cite this article

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 somatostatin10–12 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 secretion18,19 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.

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Authors and Affiliations

  1. Neuroscience Branch, Addiction Research Center, National Institute on Drug Abuse, Baltimore, Maryland, 21224, USA

    Errol B. De Souza & Michael J. Kuhar

  2. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

    Errol B. De Souza, Peter J. Whitehouse, Michael J. Kuhar & Donald L. Price

  3. Neuropathology Laboratory, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA

    Peter J. Whitehouse & Donald L. Price

  4. Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California, 92037, USA

    Wylie W. Vale

Authors
  1. Errol B. De Souza
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  2. Peter J. Whitehouse
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  3. Michael J. Kuhar
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  4. Donald L. Price
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  5. Wylie W. Vale
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De Souza, E., Whitehouse, P., Kuhar, M. et al. Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease. Nature 319, 593–595 (1986). https://doi.org/10.1038/319593a0

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