Premium
Calcium dysregulation in relation to A lzheimer‐type pathology in the ageing brain
Author(s) -
Garwood C.,
Faizullabhoy A.,
Wharton S. B.,
Ince P. G.,
Heath P. R.,
Shaw P. J.,
Baxter L.,
Gelsthorpe C.,
Forster G.,
Matthews F. E.,
Brayne C.,
Simpson J. E.
Publication year - 2013
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12033
Subject(s) - ageing , calcium , pathology , neuroscience , calcium binding protein , medicine , biology
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 Ca 2+ 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.