Cortical M1 receptor concentration increases without a concomitant change in function in Alzheimer's disease

Cassia R. Overk, Christian C. Felder, Yuan Tu, Doug A. Schober, Kelly R. Bales, Joanne Wuu, Elliott J. Mufson

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Although the M1 muscarinic receptor is a potential therapeutic target for Alzheimer's disease (AD) based on its wide spread distribution in brain and its association with learning and memory processes, whether its receptor response is altered during the onset of AD remains unclear. A novel [35S]GTPγS binding/immunocapture assay was employed to evaluated changes in M1 receptor function in cortical tissue samples harvested from people who had no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD. M1 function was stable across clinical groups. However, [3H]-oxotremorine-M radioligand binding studies revealed that the concentration of M1 cortical receptors increased significantly between the NCI and AD groups. Although M1 receptor function did not correlate with cognitive function based upon mini-mental status examination (MMSE) or global cognitive score (GCS), functional activity was negatively correlated with the severity of neuropathology determined by Braak staging and NIA-Reagan criteria for AD. Since M1 agonists have the potential to modify the pathologic hallmarks of AD, as well as deficits in cognitive function in animal models of this disease, the present findings provide additional support for targeting the M1 receptor as a potential therapeutic for AD.

Original languageEnglish (US)
Pages (from-to)63-70
Number of pages8
JournalJournal of Chemical Neuroanatomy
Volume40
Issue number1
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Keywords

  • Bmax
  • Functional activity
  • GPCR
  • MCI
  • Muscarinic receptor

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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