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

JoAnne McLaurin, Meredith E Kierstead, Mary E Brown, Cheryl A Hawkes, Mark H L Lambermon, Amie L Phinney, Audrey A Darabie, Julian E Cousins, Janet E French, Melissa F Lan, Fusheng Chen, Sydney S N Wong, Howard T J Mount, Paul E Fraser, David Westaway, Peter St George-Hyslop

Index: Nat. Med. 12(7) , 801-8, (2006)

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Abstract

When given orally to a transgenic mouse model of Alzheimer disease, cyclohexanehexol stereoisomers inhibit aggregation of amyloid beta peptide (Abeta) 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 Abeta 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 Abeta oligomers has a central role in the pathogenesis of Alzheimer disease.