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

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.

• Authors: C Garwood, A Faizullabhoy, S B Wharton, P G Ince, P R Heath, P J Shaw, L Baxter, C Gelsthorpe, G Forster, F E Matthews, C Brayne, J E Simpson, MRC Cognitive Function and Ageing Neuropathology Study Group
• Journal: Neuropathology and applied neurobiology (Neuropathol Appl Neurobiol) Vol. 39 Issue 7 Pg. 788-99 (Dec 2013) ISSN: 1365-2990 [Electronic] England
• PMID: 23421725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 British Neuropathological Society.

Chemical References

• Calcium

Topics

• Adolescent
• Adult
• Aging
• Alzheimer Disease (metabolism, pathology)
• Astrocytes (metabolism)
• Brain (metabolism, pathology)
• Calcium (metabolism)
• Child
• Female
• Humans
• Male
• Middle Aged
• Neurons (metabolism)
• Plaque, Amyloid (metabolism)
• Young Adult