Stability of dentate gyrus granule cell mossy fiber BDNF protein expression with age and resistance of granule cells to Alzheimer's disease neuropathology in a mouse model.

Declining hippocampal brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of Alzheimer's disease (AD). However, few studies have examined where hippocampal BDNF protein has its highest concentration, and plays a critical role in memory, the dentate gyrus granule cell (GC) axons (mossy fibers; MFs). Using a well-established mouse model of cerebral amyloid overexpression, the Tg2576 mouse model of AD, we found that MF BDNF did not decline with age, suggesting a notable exception to the idea that reduced hippocampal BDNF contributes to AD pathobiology. We also identified that Tg2576 GC activity correlates with MF BDNF protein based on GC expression of the transcription factor ΔFosB. These data are consistent with the activity-dependence of MF BDNF. In addition, we found that Tg2576 GCs were relatively resistant to accumulation of amyloid-b, providing insight into AD resilience, which has strong therapeutic implications.