Expression of Ki67, PCNA and the chromosome replication licensing protein Mcm2 in glial cells of the ageing human hippocampus increases with the burden of Alzheimer-type pathology

Cell-cycle mechanisms may be aberrantly reactivated in the ageing brain and associated with the development of pathology, including Alzheimer's disease. Activation of cell-cycle mechanisms in glia has, however, been little studied. Our aim was to determine whether expression of a marker for chromosomal replication licensing, Mcm2, occurs in glia of the ageing hippocampus, and to compare its expression to that of Ki67 and PCNA. Blocks of hippocampus were obtained from 19 elderly brains derived from the MRC-CFAS neuropathology cohort, which included a spectrum of Alzheimer-type pathology, semi-quantified using the Braak scoring system for neurofibrillary tangles. Mcm2, PCNA and Ki67 were detected immunohistochemically. Expression of Mcm2, Ki67 and PCNA was observed in glial cells and neurons, with a trend to increased expression in association with higher burdens of Alzheimer-type pathology. Mcm2 expression in glial cells showed a significant linear trend across Braak stages (P = 0.043). This study demonstrates that grey and white matter glial cells show expression of cell-cycle markers in the ageing brain and that re-licensing for chromosomal replication is a component of the mechanisms activated. A quantitative relationship to the burden of Alzheimer-type pathology suggests that cell-cycle re-entry in glial cells may be important in the pathogenesis of age-related neurodegeneration.