Glial Activation In A Beta Pp/Ps1 Mice Is Associated With Infiltration Of Ifn Gamma-Producing Cells

Whereas the classical histological hallmarks of Alzheimer's disease (AD) are deposition of amyloid-containing plaques and development of neurofibrillary tangles, there is also clear evidence of inflammatory changes accompanied by the presence of activated microglia and astrocytosis. However, at this time, it remains uncertain whether inflammatory changes contribute to pathogenesis of the disease or if they are secondary to deposition of amyloid-beta or other pathological changes. A greater understanding of the sequence of events would clearly improve development of strategies to delay progression of the disease. There is a realistic expectation that advances in imaging technology may provide the key to uncovering this sequence. In this study, we employed non-invasive imaging techniques to examine changes in tissue state in hippocampus and cortex of transgenic mice which overexpress amyloid-beta protein precursor and presenilin 1 and show that the observed increase in T-1 relaxation time was associated with astrogliosis while the decrease in T-2 relaxation time was associated with microglial activation. We explored the possibility that interferon-gamma might trigger glial activation and demonstrate a genotype-related infiltration of macrophages and natural killer cells, which release interferon-gamma. The evidence suggests that IFN gamma triggers glial activation and expression of proinflammatory cytokines, and these changes, in turn, contribute to the decrease in long-term potentiation.