Differential Regulation of Molecular Subtypes of Muscarinic Receptors in Alzheimer's Disease

Donna D. Flynn, Gaby Ferrari‐DiLeo, Deborah C. Mash, Allan I. Levey

Research output: Contribution to journalArticlepeer-review

199 Scopus citations

Abstract

Molecular subtypes of muscarinic receptors (m1-m5) are novel targets for cholinergic replacement therapies in Alzheimer's disease. However, the status of these receptors in human brain and Alzheimer's disease is incompletely understood. The m1-m5 receptors in brains from control subjects and Alzheimer's disease patients were examined using a panel of specific antisera and radioligand binding. Quantitative immunoprecipitation demonstrated a predominance of the m1, m2, and m4 receptor subtypes in cortical and subcortical regions in control subjects. In Alzheimer's disease, normal levels of m1 receptors measured by radioligand binding contrasted with decreased m1 receptor immunoreactivity, suggesting that the m1 receptor is altered in Alzheimer's disease. The m2 immunoreactivity was decreased, consistent with the loss of m2 binding sites and the location of this receptor subtype on presynaptic cholinergic terminals. The m4 receptor was up-regulated significantly and may offer a target for new memory-enhancing drugs. Differential alterations of molecular subtypes of muscarinic receptors may contribute to the cholinergic component of Alzheimer's disease dementia.

Original languageEnglish (US)
Pages (from-to)1888-1891
Number of pages4
JournalJournal of neurochemistry
Volume64
Issue number4
DOIs
StatePublished - Apr 1995

Keywords

  • Alzheimer's disease
  • Muscarinic receptor subtypes
  • Receptor regulation
  • Receptor subtype-specific antisera
  • Therapeutic targets

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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