Neuronal activity regulates the regional vulnerability to amyloid-? deposition.

ABSTRACT: Amyloid-? (A?) plaque deposition in specific brain regions is a pathological hallmark of Alzheimer's disease. However, the mechanism underlying the regional vulnerability to A? deposition in Alzheimer's disease is unknown. Herein, we provide evidence that endogenous neuronal activity regulates the regional concentration of interstitial fluid (ISF) A?, which drives local A? aggregation. Using in vivo microdialysis, we show that ISF A? 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?, and unilateral vibrissal deprivation decreased ISF A? 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? deposition in Alzheimer's disease.

SUBMITTER: Bero AW 

PROVIDER: S-EPMC3102784 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature