Impaired cell proliferation in the subventricular zone in an Alzheimer's disease model.

In mammalian central nervous system, neurogenesis occurs in the hippocampus and the subventricular zone (SVZ). We used triple transgenic mouse model of Alzheimer's disease (3 x Tg-AD) harbouring three mutant genes (beta-amyloid precursor, presenilin-1 and tau) and their controls (non-Tg) from 2 to 12 months of age to establish the link between AD and SVZ neurogenesis. We determined the number of SVZ proliferating cells by the presence of phosphorylated histone H3, and their colocalization with glial fibrillary acidic protein to exclude glial phenotype. Less than 2% of histone H3-labelled cells displayed glial fibrillary acidic protein. 3 x Tg-AD mice showed a significant reduction in cell proliferation from 3 months of age that was sustained through all ages, compared with controls. These results indicate that 3 x Tg-AD mice have impaired SVZ cell proliferation, which exacerbates with age.