Apolipoprotein D mRNA expression is elevated in PDAPP transgenic mice

Apolipoprotein D (apoD) expression is known to be elevated in select region s of rodent and human brain in association with different types of CNS path ology. To investigate a potential role for apoD in the neuropathology of Al zheimer's disease, we have measured apoD mRNA expression in transgenic mice expressing mutated human amyloid precursor protein under control of platel et-derived growth factor promoter (PDAPP mice), In situ hybridization analy sis revealed increased apoD mRNA expression in brains of aged (26 months) P DAPP transgenic mice compared to aged littermate controls. These increases were most prominent in the hippocampal fimbria, corpus callosum and other w hite matter tracts. No substantial increases in expression were observed in white matter regions in young (6 months) PDAPP transgenic mice compared to young controls. Comparison between aged and young control mice revealed in creased apoD expression in similar white matter regions of the aged animals . These findings suggest that, although increases in apoD expression are a normal feature of brain aging, super-increases may represent a glial cell c ompensatory response to beta-amyloid deposition in Alzheimer's disease.