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J Biol Chem. 2015 Jan 23;290(4):1966-78. doi: 10.1074/jbc.M114.586602. Epub 2014 Dec 2.

A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid β in the brain in a transgenic model of Alzheimer disease.

Author information

1
From the Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease.
2
BioMEMS Resource Center, Massachusetts General Hospital.
3
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, and.
4
Pediatrics Services, Harvard Medical School Charlestown, Massachusetts 02129.
5
From the Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, ehudry@partners.org.

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.

KEYWORDS:

Aggregation; Alzheimer Disease; Amyloid β (AB); Cromolyn Sodium; asthma; in vivo microdialysis; mouse

PMID:
25468905
PMCID:
PMC4303653
DOI:
10.1074/jbc.M114.586602
[Indexed for MEDLINE]
Free PMC Article

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