Altered ryanodine receptor expression in mild cognitive impairment and Alzheimer's disease.

Abstract	Intracellular Ca(2+) dysregulation is an underlying component of Alzheimer's disease (AD) pathophysiology, and recent evidence implicates the ryanodine receptor (RyR) in the disease pathway. Three genes code for different RyR isoforms and each gene transcript gives rise to several alternatively spliced messenger RNAs (mRNAs). These variants confer distinct functionality to the RyR channel, such as altering Ca(2+) release properties or subcellular localization. Changes in RyR isoform expression and alternative splicing have not been examined for potential roles in AD pathogenesis. Here, we compare mRNA levels of the RyR2 and RyR3 isoforms as well as specific alternatively spliced variants across vulnerable brain regions from postmortem samples of individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD. We find an increase in RyR2 transcripts in MCI brains compared with no cognitive impairment. In addition, there is a reduction in a RyR2 splice variant, associated with an antiapoptotic function, in MCI and AD brains. These alterations in RyR expression at early disease stages may reflect the onset of pathologic mechanisms leading to later neurodegeneration.
Authors	Angela M Bruno, Jeff Y Huang, David A Bennett, Robert A Marr, Michelle L Hastings, Grace E Stutzmann
Journal	Neurobiology of aging (Neurobiol Aging) Vol. 33 Issue 5 Pg. 1001.e1-6 (May 2012) ISSN: 1558-1497 [Electronic] United States
PMID	21531043 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright	Copyright Â© 2012 Elsevier Inc. All rights reserved.
Chemical References	Ryanodine Receptor Calcium Release Channel
Topics	Aged Aged, 80 and over Alzheimer Disease (genetics, metabolism, pathology) Cognitive Dysfunction (genetics, metabolism, pathology) Female Humans Male Ryanodine Receptor Calcium Release Channel (adverse effects, biosynthesis, genetics)

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