title: Neuronal activity regulates the regional vulnerability to amyloid-β 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.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Adam W
authors.initials: AW
authors.lastname: Bero
authors.forename: Ping
authors.initials: P
authors.lastname: Yan
authors.forename: Jee Hoon
authors.initials: JH
authors.lastname: Roh
authors.forename: John R
authors.initials: JR
authors.lastname: Cirrito
authors.forename: Floy R
authors.initials: FR
authors.lastname: Stewart
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Raichle
authors.forename: Jin-Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D045604:Extracellular Fluid; D005260:Female; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012683:Sensory Deprivation; D013003:Somatosensory Cortex / Q000473:pathology
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019344:Lactic Acid