Cancer drug bexarotene reverses Alzheimer’s deficits in mice

In two recent studies, NIA-supported investigators identified a surprising new candidate drug treatment for Alzheimer’s disease (AD) and determined a potential mechanism of action for the compound.

In the first study, researchers demonstrated that bexarotene, a skin cancer drug, reversed AD symptoms in a mouse model of the disease. Researchers at Case Western Reserve University School of Medicine in Cleveland found that within 72 hours of treatment, bexarotene reversed social, cognitive, and olfactory deficits and cleared beta amyloid—a pathological hallmark of AD—from the mice’s brains. Bexarotene treatment was effective in both early and later stages of Alzheimer’s in the mice. The investigators emphasize that while these findings are promising, there is further need for translational research from the animal studies to examine the efficacy of bexarotene in people with AD.

A second article by researchers at the Indiana University School of Medicine in Indianapolis established a potential mechanism of action for bexarotene. Investigators with the Alzheimer’s Disease Neuroimaging Initiative (ADNI) genotyped 103 ADNI participants and identified a variant of the DHCR 24 gene that was associated with lower brain amyloid levels compared to people without the gene, suggesting that this variant may have a neuroprotective effect. Researchers believe that bexarotene may act through the DHCR 24 pathway, providing further support for continued investigation of bexarotene. Specifically, these findings encourage more studies to evaluate the gene’s possible role in AD pathogenesis.


Cramer, P. E., et al. ApoE-directed therapeutics rapidly clear β-amyloid and reverse deficits in AD mouse models. Science. 2012 Mar 23;335(6075):1503-6. Epub 2012 Feb 9.

Swaminathan S., et al. Amyloid pathway-based candidate gene analysis of [11C]PiB-PET in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, Brain Imaging and Behavior, (2012) 6:1-15. 8.