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Neurobiol Dis. 2010 Jun;38(3):492-4. doi: 10.1016/j.nbd.2010.02.009. Epub 2010 Mar 2.

Thinking outside the box about COX-1 in Alzheimer's disease.

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Greater Los Angeles Healthcare System, Geriatric Research Education and Clinical Center, Veteran's Affairs Medical Center, North Hills, CA 91343, USA.


This article from Coma et al. shows that a salicylic acid derivative Triflusal, a platelet aggregation inhibitor and irreversible inhibitor of COX-1, can correct defects in axonal curvature and cognition in an AD transgenic mouse model (Tg2576) (Coma et al., 2010). Here we discuss the controversy over the role of COX-1 in AD, which has not been considered carefully in part due to the presumed adverse gastrointestinal effects of COX-1 antagonism. However, recent clinical data from this group as well as other groups challenges this assumption that COX-1 antagonism will be associated with side effects. Most importantly this article raises critical questions about the role of COX-1, versus COX-2 versus both in Abeta pathogenesis. The animal model data in this article as well as the recently published trial data suggest that COX-1 may play an important role in early pathogenesis and should not be ignored as a potential target for early intervention.

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