Copyright ã 2002 by James Michael Howard. New Support 2011 (below)
In 1985 I suggested low
dehydroepiandrosterone (DHEA) may result in Alzheimer's disease in those
vulnerable. (This was first supported in 1987.) That
is, I suggest DHEA optimizes transcription and replication of DNA, therefore, DHEA optimizes growth and development and
maintenance of all tissues, especially the brain. DHEA naturally begins to
decline around ages 20-25, slowly declining in old age to very low levels. When
DHEA declines below maintenance levels, vulnerabilities of brain function may
be exposed. Alzheimer's is one of these vulnerabilities.
Just recently, new research has appeared
which supports my hypothesis regarding DHEA and Alzheimer's disease.
Luchsinger, et al., reported that reducing caloric intake may reduce the risk
of Alzheimer's disease "in individuals carrying the apolipoprotein E
epsilon4 allele" (Archives of Neurology 2002 Aug; 59(8):
1258-63). (People with apolipoprotein E epsilon4, apoE4, are more vulnerable to
Alzheimer's disease. They develop Alzheimer's disease at an earlier age.) Roth,
et al., found that caloric restriction extends "youthful levels of
DHEAS" in nonhuman primates and suggest this may be the case in humans (Science
2002 Aug; 297: 811). (DHEAS is considered to be the source of DHEA.)
This suggests that reducing caloric intake extends the availability of DHEA; I
suggest it is this extension of DHEA that may reduce the onset of Alzheimer's disease.
In June, this year, Raber, et al., found that
"apoE4 contributes to cognitive decline by reducing AR [androgen
receptors] levels in the brain," (Journal of Neuroscience 2002 Jun;
22(12): 5204-9). Androgen receptors are molecular carriers that bind and
transport androgens into the cell nucleus. DHEA is an "active
competitor" for androgen receptors (Journal of Steroid Biochemistry
1982 Feb; 16(2): 311-5). Because people with apoE4 are advanced in the
aging process, they are affected more by the decline in DHEA.
The probability of Alzheimer's disease
increases directly with age. DHEA declines to very low levels in old age. I
suggest Alzheimer's disease results from reduced maintenance of brain function
as a result of declining DHEA. Individuals who carry the apoE4 gene are at
increased risk because apoE4 reduces the availability of DHEA to their brains
below that of their age.
New Support:
Acta
Biochim Pol. 2011 Dec 6. [Epub ahead of print] Neuroprotective effects of
dehydroepiandrosterone (DHEA) in rat model of Alzheimer's disease.
Aly HF, Metwally FM, Ahmed HH.
SourceTherapeutical Chemistry Department, National Research
Center, Cairo, Egypt.
Abstract
The
study was undertaken to elucidate a possible neuroprotective role of
dehydroepiandrosterone (DHEA) against the development of Alzheimer's disease in
experimental rat model. Alzheimer's disease was produced in young female
ovariectomized rats by intraperitoneal administration of AlCl(3)
(4.2 mg/kg body weight) daily for 12 weeks. Half of these animals also received
orally DHEA (250 mg/kg body weight, three times weekly) for 18 weeks. Control
groups of animals received either DHAE alone, or no DHEA, or were not
ovariectomized. After such treatment the animals were analyzed for oxidative
stress biomarkers such as hydrogen peroxide, nitric oxide and malondialdehyde,
total antioxidant capacity, reduced glutathione, glutathione peroxidase,
glutathione reductase, superoxide dismutase and catalase activities,
antiapoptotic marker Bcl-2 and brain derived neurotrophic factor. Also brain
cholinergic markers (acetylcholinesterase and acetylcholine) were determined.
The results revealed significant increase in oxidative stress parameters
associated with significant decrease in the antioxidant enzyme activities in
Al-intoxicated ovariectomized rats. Significant depletion in brain Bcl-2 and
brain-derived neurotrophic factor levels were also detected. Moreover,
significant elevations in brain acetylcholinesterase activity accompanied with
significant reduction in acetylcholine level were recorded. Significant
amelioration in all investigated parameters was detected as a result of
treatment of Al-intoxicated ovariectomized rats with DHEA. These results were
confirmed by histological examination of brain sections. These results clearly
indicate a neuroprotective effect of DHEA against Alzheimer's disease.