It is a neurodegenerative disorder associated with accumulation of Beta amyloid (plaque) and tau proteins (tangles).  Beta amyloid has been called the “Darth Vader” of Alzheimer’s.  5 million Americans suffer currently; in 2050, the number is estimated to range from 11-16 million.  It is the 6th leading cause of death.  Most studies show that the incidence in both men and women is the same until the age of 80, when the incidence increases in women.  Some studies show that the incidence is increased in women by up to a factor of 6.  The major risk factors- Age, Sex, Genetics, and Hormone Deficiency.

Carriers of the Apolipoprotein E-e4 gene have an increased risk, as this gene results in less breakdown of Beta amyloid in the brain.  In women, the negative effect is more pronounced.

Both estradiol and testosterone increase alpha secretase, an enzyme that prevents Beta amyloid formation; both also decrease Beta secretase, which decreases the formation of this “Darth Vader”.  Estradiol and testosterone increase neprilysin, which degrades Beta amyloid.  Testosterone and progesterone decrease hyperphosphorylation of tau proteins or the formation of tangles.

Testosterone is the major player, having a much greater effect than the other hormones.

Men with early and late stages of Alzheimer’s disease have significantly lower levels of testosterone.  Increased testosterone levels and testosterone therapy increase memory and cognition.  A study by Dr. Lu concluded that testosterone therapy increased memory and quality of life in Alzheimer’s patients.  Studies in male mice with low testosterone revealed increased Beta amyloid accumulation and behavioral impairment.  Testosterone has also been shown to improve memory and cognition in a mouse model of Alzheimer’s disease.

Dr. Edward Friedman at the University of Chicago, and other researchers believe that we may prevent Alzheimer’s disease or even reverse early Alzheimer’s, with testosterone replacement in men and testosterone with or without estradiol/progesterone in women.  It may be worthwhile to obtain his book, “How You and Your Doctor Can Fight Breast Cancer, Prostate Cancer and Alzheimer’s”. He has also recently published an excellent review “Hormones are the Answer to Alzheimer’s Disease” in 11/2018; 68 research studies are discussed!

References:  E. Friedman, 2013; E. Friedman, 11/2018; C.Pike, Journal of Neuroscience, 2006; C. Pike, Journal of Neuroscience, 1/2017; L. Baum, Journal of Gerontology, 2005; P. Lu, Archives of Neurology, 2/2006; S. Papasozomenos, PNAS, 2002; S. Davis, Clinical Endocrinology, 10/2014; L. Chu, Journal Of Alzheimer’s Disease, 2010; H. Shao, Neurology, 2012; Alzheimer’s Association, Alzheimer’s Dementia, 3/2015; M. Mielke, Clinical Epidemiology, 2014