Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse Alzheimer phenotype in a mouse model.
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.
McLaurin
JoAnne
J
Centre for Research in Neurodegenerative Diseases, 6 Queen's Park Crescent West, Toronto, Ontario M5S 3H2 Canada. j.mclaurin@utoronto.ca
Kierstead
Meredith E
ME
Brown
Mary E
ME
Hawkes
Cheryl A
CA
Lambermon
Mark H L
MH
Phinney
Amie L
AL
Darabie
Audrey A
AA
Cousins
Julian E
JE
French
Janet E
JE
Lan
Melissa F
MF
Chen
Fusheng
F
Wong
Sydney S N
SS
Mount
Howard T J
HT
Fraser
Paul E
PE
Westaway
David
D
St George-Hyslop
Peter
P
D000544:Alzheimer Disease / Q000235:genetics* / Q000517:prevention & control; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000187:drug effects; D000818:Animals; D003511:Cyclohexanols / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018697:Nootropic Agents / Q000627:therapeutic use; D010641:Phenotype; D058225:Plaque, Amyloid / Q000187:drug effects / Q000473:pathology; D013569:Synapses / Q000473:pathology / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D003511:Cyclohexanols; D018697:Nootropic Agents