1 September 2012
Testosterone and DHEA are Directly Involved in Alzheimer’s Disease. This explanation is relevant within an evolutionary context. I think mammals evolved because of natural selection for dehydroepiandrosterone (DHEA) . This is based on my principal hypothesis that DHEA increases replication and transcription of DNA, that is, DHEA increases gene activation. Furthermore, I think primates and humans evolved within mammals because of natural selection of testosterone with the maximum effect occurring in humans [2,3].The positive effect which testosterone promotes is increased androgen receptor formation. Since DHEA utilizes androgen receptors, testosterone increases entrance of DHEA and, therefore, gene activity. This change in gene activity causes differential growth in the brain as well as the body and may be the basis for sex differences. In the evolution of primates/humans, maternal testosterone increases androgen receptors in fetal brains. This increases gene activity and, therefore, bigger brains. This effect in humans, probably, first appeared in Homo erectus, or whatever hominid is now considered the origin of Homo in which male/female size differences were first reduced. The size difference between male and female H. erectus was reduced by an increase in females. The effect was a result of dramatic increase in females of higher testosterone.
The increased hominid, maternal testosterone exaggerated the ongoing primate increase in testosterone which produced a brain large enough to produce competition for DHEA, via androgen receptors, between the body and the brain. As the brain enlarged during this competition, it enlarged at the expense of the body; our brains grew bigger and our bodies became more gracile.
My point is that testosterone and DHEA combine to produce a brain and maintain it. In 1985, I first suggested that low DHEA was involved in Alzheimer’s disease . Subsequently, I decided that testosterone evolved to increase use of DHEA by all tissues, especially the brain. As far as I can determine, the first reports of low DHEA in Alzheimer’s disease appeared in 1987  and then in 1989 [6-8].
The reason women exhibit more Alzheimer’s disease is lower testosterone and DHEA. Since both testosterone and DHEA decline naturally with age, genes with less than robust formation, which are involved with brain function, will malfunction during the natural decline of testosterone and DHEA. Many will develop Alzheimer’s disease in old age, but not all. Moreover, individuals with vulnerable genes may exhibit the disease early on when testosterone and DHEA first begin to decline significantly. This is “early onset Alzheimer’s disease.”
James Michael Howard
 Howard J (2001) Hormones in mammalian evolution. Riv Biol 94, 177-183.
 Howard JM (2002) "Mitochondrial Eve," "Y Chromosome Adam," testosterone, and human evolution. Riv Biol 95, 319-325.
 Howard J (2001) Androgens in human evolution. A new explanation of human evoluation. Riv Biol 94, 345-362.
 Howard JM (1985) A theory of the control of the ontogeny and phylogeny of Homo sapiens by the interaction of dehydroepiandrosterone and the amygdala. United States Copyright Office, Registration Number: TXu00022058.
 Bologa L, Sharma J, Roberts E (1987) Dehydroepiandrosterone and its sulfated derivative reduce neuronal death and enhance astrocytic differentiation in brain cell cultures. J Neurosci Res 17, 225-234.
 Sunderland T, Merril CR, Harrington MG, Lawlor BA, Molchan SE, Martinez R, Murphy DL (1989) Reduced plasma dehydroepiandrosterone concentrations in Alzheimer's disease. Lancet 2, 570.
 Mohan PF (1989) Dehydroepiandrosterone and Alzheimer's disease. Lancet 2, 1048-1049.
 Svec F, Lopez A (1989) Antiglucocorticoid actions of dehydroepiandrosterone and low concentrations in Alzheimer's disease. Lancet 2, 1335-1336.