Neuronal activity regulates the regional vulnerability to amyloid-β deposition

AW Bero, P Yan, JH Roh, JR Cirrito, FR Stewart… - Nature …, 2011 - nature.com
Nature neuroscience, 2011nature.com
Amyloid-β (Aβ) plaque deposition in specific brain regions is a pathological hallmark of
Alzheimer's disease. However, the mechanism underlying the regional vulnerability to Aβ
deposition in Alzheimer's disease is unknown. Herein, we provide evidence that
endogenous neuronal activity regulates the regional concentration of interstitial fluid (ISF)
Aβ, which drives local Aβ aggregation. Using in vivo microdialysis, we show that ISF Aβ
concentrations in several brain regions of APP transgenic mice before plaque deposition …
Abstract
Amyloid-β (Aβ) plaque deposition in specific brain regions is a pathological hallmark of Alzheimer's disease. However, the mechanism underlying the regional vulnerability to Aβ deposition in Alzheimer's disease is unknown. Herein, we provide evidence that endogenous neuronal activity regulates the regional concentration of interstitial fluid (ISF) Aβ, which drives local Aβ aggregation. Using in vivo microdialysis, we show that ISF Aβ 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 Aβ, and unilateral vibrissal deprivation decreased ISF Aβ 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 Aβ deposition in Alzheimer's disease.
nature.com