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Bexarotene may exert Beneficial Effects of Reducing Beta-Amyloid by Increasing Testosterone (James Michael Howard, Fayetteville, Arkansas)

(Science 2012: "ApoE-Directed Therapeutics Rapidly Clear beta-Amyloid and Reverse Deficits in AD Mouse Models," Cramer, et al., report that "...RXR [retinoid X receptor] activation [by bexarotene] stimulates physiological Aß [beta-amyloid] clearance mechanisms, resulting in the very rapid reversal of a broad range of Aß-induced deficits."

Bexarotene is a "retinoid x receptor agonist." Research suggests that stimulation of estradiol and testosterone may involve "retinoid X receptor signaling." (Endocrinology. 2009 Sep;150(9):4260-9). I could not find any research connecting bexarotene with estradiol or testosterone.

Low testosterone and estradiol have been found in Alzheimer's disease and have been identified as potential sources of Alzheimer's disease. Moreover, testosterone and estrogen have been found to reduce beta-amyloid formation (Front Neuroendocrinol. 2009 Jul;30(2):239-58).

I suggest the positive effects that bexarotene produces in reducing beta-amyloid in mice may be due to increases primarily in testosterone and estradiol. Research supports reduced beta-amyloid accumulation in mice caused more bytestosterone than estradiol(Brain Res. 2010 Nov 4;1359:281-90). Alzheimer's occurs more in women than men.

It is my hypothesis of 1985 that low DHEA may be the cause of Alzheimer's disease. I think the evolutionary function of the sex hormones is induction of cellular receptors which participate in the absorption and use of DHEA for cellular function. There are indications that DHEA produces positive actions against the effects of beta-amyloid neurotoxicity (Neuropsychiatr Dis Treat. 2008 Feb;4(1):209-18). I could not find any research connecting bexarotene with DHEA.)

James Howard of AR 1:15PM February 10, 2012