Biology 202
2000 Second Web Report
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Established risk factors for Alzheimer's disease include family history and increasing age. As research continues, however, head trauma, exposure to aluminum, hyperthyroidism, smoking, hypertension, heart disease, alcohol consumption, and diabetes are also receiving support as possibilities. Low levels of estrogen have been cited as a factor, based on the fact women are much more likely to develop the disease and their levels of estrogen decrease in their postmenopausal years (2). A common opinion is that estrogen enters cells and then affects the nucleus to regulate genes (3). Newer research suggests that estrogen may also promote growth of neurons, much like nerve growth factor, and "share signaling pathways with neutrophins" (1). Indeed, cognitive studies show that women taking an estrogen supplement improve performance on memory tasks.

The discovery that estrogen may help nerve growth was made early in the 1970's when it was shown to incite development in axons and dendrites in the brain slices (1). This growth aids in communication by maintaining synaptic connections and promoting survival of neurons (4). Additionally, estrogen may promote an increase in levels of acetylcholine containing neurons. Acetylcholine deficiency is thought to be another cause of the debilitating dementia, because it is the neurotransmitter most involved with cognitive abilities.

"Estogen binding to estrogen receptors in cerebral cortical neurons" (1)

A recent study (5) has shown that estrogen patches improved the memory of mildly and moderately demented women within a week of treatment and subsided upon withdrawal of the hormone. Estrogen receptors are found in the hippocampus and cerebral cortex where the hormone is able to stimulate growth of connections between and "clean" the brain of free radicals (6). In one study, 1124 elderly women were followed for 1 to 5 years. The study found that only 6% of the women using estrogen had developed Alzheimer's disease as opposed to 16% of the population who had not taken the hormone. Also noted, was that if women on estrogen did develop the disease, they did so much later (7).

Much attention has been given to the biological aspects of Alzheimer's disease in order to treat or possibly prevent it. The initial discoveries of plaques and tangles made by Alois Alzheimer nearly a century ago have been further investigated and led to many important findings in neuroscience. New research has shown that estrogen may have an effect on amyloid plaques, insoluble deposits of beta-amyloid and fragments of cellular material deposited around neurons. Beta-amyloid is a sticky portion of APP, or amyloid precursor protein, that quickly clumps, then forming plaques in the tissue. A common thought is that beta-amyloid is toxic to the brain, causing inflammation or aiding in the release of free radicals. Estrogen works to prevent the deposition of the beta-amyloid plaques (2).

"Estrogen receptor mRNA in the neurons of the cerebral cortex" (1)

The brain structures affected by plaques and tangles provide much information concerning the cognitive decline seen in Alzheimer's patients. Both senile plaques and neurofibrillary tangles are found in the prefrontal cortex, the temporal association cortex, and the hippocampus, but may also be found in the basal forebrain, the amygdala, and catecholaminergic nuclei. PET scans have shown significant decline in the cerebral metabolism of the frontal, temporal, and parietal areas, but estrogen has been shown to improve blood circulation in the brain based on animals testing. In addition, the hippocampus, responsible for the consolidation and storage of memory, may also be aided by estrogen to "maintain the integrity of the hippocampus" (2). Furthermore, a study performed on rats discovered that estrogen prevents atrophy of neurons in this area (4).

Currently, there is no cure for Alzheimer's disease, but new strides in research continue to improve the hope that some day treatment and prevention of the disease will be possible. Popular choices in treatment include cholinesterase inhibitors, vitamin E, and anti-inflammatory agents. Findings now show that hormone replacement strengthens the effectiveness of cholinesterase inhibitors (8). The excitement over discoveries concerning estrogen, however, should be approached carefully. Hormone replacement increases the risk of breast cancer in women and has feminizing effects on men. Yet, estrogen also has the benefits of preventing osteoporosis and cardiovascular disease. Must it come down to choosing which ailment to die from?

Most hormone replacement therapies for postmenopausal women are a combination of estrogen and progesterone. It is now thought that the progesterone may be producing the increased risks of cancer. Estrogen, however, cannot be given alone except to women who have had hysterectomies, because of an overwhelming increase in risk of endometrial cancer. One post menopausal woman I spoke to about this issue said that she would undergo the operation in order to take the estrogen alone and lower the risks of all the diseases. Will this be a viable option someday? If biomedicine has the capability to lower the chances of getting these devastating diseases, should hormone replacement therapy be protocol for older women? Most experts say that, to date, studies have been too biased to make this broad kind of claim. Subject groups are another confound of these experiments. The women who choose "[hormone replacement therapy] tend to be more educated that those who do not, for example, and higher educational status is known to be associated with reduced risk of Alzheimer's" (8).

As the population ages, researchers in both the cognitive and biological sciences must labor to determine how a disease like Alzheimer's can be managed and, one day, cured. Estrogen appears to be an important path for research to follow in order to prevent the disease. One day, hopefully, new forms of the hormone may be developed that do not possess the dramatic side effects we see today. In this way, hormone replacement therapy may be offered to a larger population, so more people may reap the benefits of estrogen. Then, no one will have to choose which ailment to die from.

WWW Sources

2)Alzheimers.com, comprehensive site on Alzheimer's disease

3)P & S: Estrogen and Alzheimer's, from the journal Biomedical Frontiers

4)Estrogen Treatment for Alzheimer's Disease, Neurochemistry term paper

5)Estrogen: A key to Alzheimer's disease?, from the journal BioScience

6)The Alzheimer's Lottery, from the journal Natural History

7)A New Weapon Against Alzheimer's?, from Science Magazine

8)Hold Off on Estrogen for Alzheimer's Disease, from Medscape

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