Health

Seeking the Source of Alzheimer’s Disease with Ground Breaking Study

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Synapse in brainThe question over the exact causes of Alzheimer’s disease has long been at the heart of research into the condition that affects so many of our loved ones. In a recent article by Lauren Horne, she details new research into the cause and possible treatment of Alzheimer’s disease. The study that was published in June 2014 in “Nature Medicine,” the well respected medical journal, examines the theorized effect of reactive astrocytes in the development of the disease. The study was carried out under the auspices of Drs. C. Justin Lee and Daesoo Kim in Korea and their paper was published with the title: “GABA from reactive astrocytes impairs memory in mouse models of Alzheimer’s disease.”

As described in the title of the paper, the focus of this research was centered around the effects of the reactive astrocytes. In particular, Lee and Kim pointed to the fact that these reactive astrocytes are often found in large percentages in the brains of patients with Alzheimer’s disease and are known to produce GABA, a neurotransmitter inhibitor. As they found that the reactive astrocytes were producing the GABA through Monoamine oxidase B(MAO-B), an enzyme that then passed on the GABA into the system through the BESt1 channel, they decided to target the B(MAO-B) in their testing.

What they found was that when they used the Parkinson’s disease drug Selegiline as an inhibitor to bring the levels of the GABA back to more normal numbers, they were able to succeed in slowing down the firing of neurons in the brain. In their tests that they carried out on mice with Alzheimer’s disease in the labs, those subjects who received the inhibitor treatment exhibited signs of improved memory that were consistent with their theory.

Unfortunately these results did not leave any lasting changes on the mice as the effect of the drugs wore off. However, to all those who are invested in finding a cure for Alzheimer’s disease, this study has provided valuable knowledge and new insights that may soon lead to a treatment.

Michael Mullan: Sex Differences in Alzheimer’s Disease

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Illustration to go with the review of the book, "Brainstorm: The Flaws in the Science of Sex Differences" by Rebecca Jordan-Young
Illustration to go with the review of the book, “Brainstorm: The Flaws in the Science of Sex Differences” by Rebecca Jordan-Young

Article Written by Dr. Michael Mullan

There has long been controversy over whether women or men are most affected by Alzheimer’s disease. Decades ago the perceived wisdom was that Alzheimer’s affected women more than men because women live longer than men and Alzheimer’s is a disease of aging. However, this apparent sex discrimination was challenged in subsequent studies and more recent investigations suggest that women may be at greater risk than men on an age matched basis. However, even this is controversial and may differ between populations.

For instance, some American studies report equal rates between men and women whereas European ones report a sex difference with more women than men being affected. However, several incidence studies looking at new cases of Alzheimer’s suggests that women are more readily affected than men.

Many reasons have been offered as to why there may be sex discrimination by Alzheimer pathology. One idea is that loss of sex hormones after menopause is particularly detrimental to the human brain. It’s known, for instance, that sex hormones can regulate Beta amyloid production. Cell culture studies show that estrogen and testosterone can mitigate the production of amyloid, one of the central features of Alzheimer’s.

Sex hormones may play other roles as well as regulating the amount of amyloid produced. They may have a role for instance in the breakdown of amyloid and the clearance of amyloid by other mechanisms in the brain. It’s also possible that progesterone have a protective role in the brain. Evidence suggests that after difference insults to the brain, progesterone can be protective.

While all of these observations on the sex differences have been very valuable, no therapy has yet emerged based on hormone replacement. In fact, key studies looking at hormone replacement in post-menapausal women have not shown any beneficial reduction in the risk for Alzheimer’s disease. At best, hormone replacement therapy has shown mixed results in relation to any protection against Alzheimer’s disease. Interestingly, any evidence that sex hormones are helpful in Alzheimer’s are restricted to prevention strategies rather than treatment strategies. In other words, it looks as if prolonged exposure to sex hormones may influence the rate of Alzheimer’s disease; but, once the disease is established, sex hormone therapy is not clearly protective.
So, although there is evidence that Alzheimer’s disease does indeed discriminate against women, the underlying causes are still uncertain and simple hormone replacement therapy may not be the best answer. However, more broadly, Alzheimer’s discriminates against both genders once natural hormone levels start to fall in the later decades of life.

Much more work needs to be done to understand these effects and to ask whether any of these findings can be turned into new clinical treatments for the disease.