Calcium dysregulation in relation to A lzheimer‐type pathology in the ageing brain

Abstract

Aims: Calcium dyshomeostasis is implicated in the pathogenesis of several neurodegenerative disorders including A lzheimer'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 Ca2+ signalling pathway in astrocytes as A lzheimer‐type pathology developed. In this study we sought to determine the expression of calpain‐10 and calcium/calmodulin‐dependent kinase alpha (CamKII α) in relation to A lzheimer‐type pathology in a population‐based study. Methods: Using post mortem temporal cortex samples derived from the M edical R esearch C ouncil C ognitive F unction and A geing St udy (MRC‐CFAS) ageing brain cohort we examined calpain‐10 and CamKII α 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 B raak 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 A lzheimer‐type pathology. In addition, we identify a subpopulation of calpain‐10 immunoreactive interlaminar astrocytes that extend processes deep into the cortex. CamKII α 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 A lzheimer‐type pathology in the ageing brain, highlighting the need for further functional studies of astrocytic calcium signalling with respect to disease progression.