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Neuropathol Appl Neurobiol. 2013 Dec;39(7):788-99. doi: 10.1111/nan.12033.

Calcium dysregulation in relation to Alzheimer-type pathology in the ageing brain.

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1
Sheffield Institute for Translational Neuroscience, Department of Neuroscience, University of Sheffield, Sheffield, UK.

Abstract

AIMS:

Calcium dyshomeostasis is implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease. However, much of the previous research has focused on changes in neuronal calcium signalling. In a recent microarray study we identified dysregulation of several key signalling pathways including the Ca(2+) signalling pathway in astrocytes as Alzheimer-type pathology developed. In this study we sought to determine the expression of calpain-10 and calcium/calmodulin-dependent kinase alpha (CamKIIα) in relation to Alzheimer-type pathology in a population-based study.

METHODS:

Using post mortem temporal cortex samples derived from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) ageing brain cohort we examined calpain-10 and CamKIIα gene and protein expression using quantitative polymerase chain reaction and immunohistochemistry.

RESULTS:

We demonstrate that astrocytic expression of calpain-10 is up-regulated, and CamKIIα down-regulated with increasing Braak stage. Using immunohistochemistry we confirm protein expression of calpain-10 in astrocytes throughout the temporal cortex and demonstrate that calpain-10 immunoreactivity is correlated with both local and global measures of Alzheimer-type pathology. In addition, we identify a subpopulation of calpain-10 immunoreactive interlaminar astrocytes that extend processes deep into the cortex. CamKIIα is predominantly neuronal in localization and is associated with the presence of diffuse plaques in the ageing brain.

DISCUSSION:

Dysregulated expression of key calcium signalling molecules occurs with progression of Alzheimer-type pathology in the ageing brain, highlighting the need for further functional studies of astrocytic calcium signalling with respect to disease progression.

KEYWORDS:

Alzheimer-type pathology; astrocytes; calcium; calcium/calmodulin-dependent kinase IIα; calpain-10

PMID:
23421725
DOI:
10.1111/nan.12033
[Indexed for MEDLINE]
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