title: A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid β in the brain in a transgenic model of Alzheimer disease.
abstract: Interfering with the assembly of Amyloid β (Aβ) peptides from monomer to oligomeric species and fibrils or promoting their clearance from the brain are targets of anti-Aβ-directed therapies in Alzheimer disease. Here we demonstrate that cromolyn sodium (disodium cromoglycate), a Food and Drug Administration-approved drug already in use for the treatment of asthma, efficiently inhibits the aggregation of Aβ monomers into higher-order oligomers and fibrils in vitro without affecting Aβ production. In vivo, the levels of soluble Aβ are decreased by over 50% after only 1 week of daily intraperitoneally administered cromolyn sodium. Additional in vivo microdialysis studies also show that this compound decreases the half-life of soluble Aβ in the brain. These data suggest a clear effect of a peripherally administered, Food and Drug Administration-approved medication on Aβ economy, supporting further investigation of the potential long-term efficacy of cromolyn sodium in Alzheimer disease.
authors.affiliation: From the Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hori
authors.affiliation: From the Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease.
authors.forename: Shuko
authors.initials: S
authors.lastname: Takeda
authors.affiliation: BioMEMS Resource Center, Massachusetts General Hospital.
authors.forename: Hansang
authors.initials: H
authors.lastname: Cho
authors.affiliation: From the Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wegmann
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, and.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Shoup
authors.affiliation: Pediatrics Services, Harvard Medical School Charlestown, Massachusetts 02129.
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: BioMEMS Resource Center, Massachusetts General Hospital.
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, and.
authors.forename: David R
authors.initials: DR
authors.lastname: Elmaleh
authors.affiliation: From the Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease.
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.affiliation: From the Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, ehudry@partners.org.
authors.forename: Eloise
authors.initials: E
authors.lastname: Hudry
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D004205:Cromolyn Sodium / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D017277:Drug Approval; D005419:Flavonoids / Q000737:chemistry; D044948:Flavonols; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000378:metabolism*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D016229:Amyloid beta-Peptides; D005419:Flavonoids; D044948:Flavonols; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C017875:fisetin; D004205:Cromolyn Sodium
keywords: Aggregation; Alzheimer Disease; Amyloid β (AB); Cromolyn Sodium; asthma; in vivo microdialysis; mouse