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

Document Type

Article

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. © 2010 Elsevier B.V.

Keywords

Bmax, Functional activity, GPCR, MCI, Muscarinic receptor

Publication Date

9-1-2010

Publication Title

Journal of Chemical Neuroanatomy

ISSN

08910618

Volume

40

Issue

1

First Page

63

Last Page

70

PubMed ID

20347961

Digital Object Identifier (DOI)

10.1016/j.jchemneu.2010.03.005

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