Neuronal activity regulates the regional vulnerability to amyloid-β deposition

Amyloid-beta (A beta) plaque deposition in specific brain regions is a pathological hallmark of Alzheimer's disease. However, the mechanism underlying the regional vulnerability to A beta deposition in Alzheimer's disease is unknown. Herein, we provide evidence that endogenous neuronal activity regulates the regional concentration of interstitial fluid (ISF) A beta, which drives local A beta aggregation. Using in vivo microdialysis, we show that ISF A beta concentrations in several brain regions of APP transgenic mice before plaque deposition were commensurate with the degree of subsequent plaque deposition and with the concentration of lactate, a marker of neuronal activity. Furthermore, unilateral vibrissal stimulation increased ISF A beta, and unilateral vibrissal deprivation decreased ISF A beta and lactate, in contralateral barrel cortex. Long-term unilateral vibrissal deprivation decreased amyloid plaque formation and growth. Our results suggest a mechanism to account for the vulnerability of specific brain regions to A beta deposition in Alzheimer's disease.