Synaptic activity regulates interstitial fluid amyloid-β levels in vivo

Aggregation of the amyloid-beta (A beta) peptide in the extracellular space of the brain is central to Alzheimer's disease pathogenesis. A beta aggregation is concentration dependent and brain region specific. Utilizing in vivo microdialysis concurrently with field potential recordings, we demonstrate that A beta levels in the brain interstitial fluid are dynamically and directly influenced by synaptic activity on a timescale of minutes to hours. Using an acute brain slice model, we show that the rapid effects of synaptic activity on A beta levels are primarily related to synaptic vesicle exocytosis. These results suggest that synaptic activity may modulate a neurodegenerative disease process, in this case by influencing A beta metabolism and ultimately region-specific A beta deposition. The findings also have important implications for treatment development.