Title | Neuronal activity regulates the regional vulnerability to amyloid-β deposition. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Bero, AW, Yan, P, Roh, JHoon, Cirrito, JR, Stewart, FR, Raichle, ME, Lee, J-M, Holtzman, DM |
Journal | Nat Neurosci |
Volume | 14 |
Issue | 6 |
Pagination | 750-6 |
Date Published | 2011 Jun |
ISSN | 1546-1726 |
Keywords | Alzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Cerebral Cortex, Disease Models, Animal, Extracellular Fluid, Female, Lactic Acid, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microdialysis, Neurons, Plaque, Amyloid, Sensory Deprivation, Somatosensory Cortex |
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. |
DOI | 10.1038/nn.2801 |
Alternate Journal | Nat. Neurosci. |
PubMed ID | 21532579 |
PubMed Central ID | PMC3102784 |
Grant List | AG029524 / AG / NIA NIH HHS / United States AG033452 / AG / NIA NIH HHS / United States AG13956 / AG / NIA NIH HHS / United States AG568127 / AG / NIA NIH HHS / United States F31 AG033452-03 / AG / NIA NIH HHS / United States K01 AG029524 / AG / NIA NIH HHS / United States K01 AG029524-05 / AG / NIA NIH HHS / United States NS06833 / NS / NINDS NIH HHS / United States NS32636 / NS / NINDS NIH HHS / United States NS67905 / NS / NINDS NIH HHS / United States P30 NS057105 / NS / NINDS NIH HHS / United States P30 NS057105-05 / NS / NINDS NIH HHS / United States P30NS057105 / NS / NINDS NIH HHS / United States R37 AG013956 / AG / NIA NIH HHS / United States R37 AG013956-16 / AG / NIA NIH HHS / United States |
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