Synaptic activity regulates interstitial fluid amyloid-β levels in vivo

John R. Cirrito, Kelvin A. Yamada, Mary Beth Finn, Robert S. Sloviter, Kelly R. Bales, Patrick C. May, Darryle D. Schoepp, Steven M. Paul, Steven Mennerick, David M. Holtzman

Research output: Contribution to journalArticle

742 Scopus citations

Abstract

Aggregation of the amyloid-β (Aβ) peptide in the extracellular space of the brain is central to Alzheimer's disease pathogenesis. Aβ aggregation is concentration dependent and brain region specific. Utilizing in vivo microdialysis concurrently with field potential recordings, we demonstrate that Aβ 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 Aβ 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 Aβ metabolism and ultimately region-specific Aβ deposition. The findings also have important implications for treatment development.

Original languageEnglish
Pages (from-to)913-922
Number of pages10
JournalNeuron
Volume48
Issue number6
DOIs
StatePublished - Dec 22 2005

Fingerprint Dive into the research topics of 'Synaptic activity regulates interstitial fluid amyloid-β levels in vivo'. Together they form a unique fingerprint.

  • Cite this