Cyclohexanehexol inhibitors of Aβ aggregation prevent and reverse Alzheimer phenotype in a mouse model

McLaurin, Jo Anne and Kierstead, Meredith E. and Brown, Mary E. and Hawkes, Cheryl A. and Lambermon, Mark H.L. and Phinney, Amie L. and Darabie, Audrey A. and Cousins, Julian E. and French, Janet E. and Lan, Melissa F. and Chen, Fusheng and Wong, Sydney S.N. and Mount, Howard T.J. and Fraser, Paul E. and Westaway, David and George-Hyslop, Peter St (2006) Cyclohexanehexol inhibitors of Aβ aggregation prevent and reverse Alzheimer phenotype in a mouse model. Nature Medicine, 12 (7). pp. 801-808. ISSN 1078-8956

Abstract

When given orally to a transgenic mouse model of Alzheimer disease, cyclohexanehexol stereoisomers inhibit aggregation of amyloid β peptide (Aβ) into high-molecular-weight oligomers in the brain and ameliorate several Alzheimer disease-like phenotypes in these mice, including impaired cognition, altered synaptic physiology, cerebral Aβ pathology and accelerated mortality. These therapeutic effects, which occur regardless of whether the compounds are given before or well after the onset of the Alzheimer disease-like phenotype, support the idea that the accumulation of Aβ oligomers has a central role in the pathogenesis of Alzheimer disease.