Preventing Alzheimer’s Disease?

I’ve been asked to comment on this article: Astaxanthin: A Rising Star in Alzheimer’s Prevention. I am happy to do so.

Whenever I see an article like this one, that touts a new “cure”(or in this case, a new preventative) for Alzheimer’s disease, my first reaction is always distrust. There are entirely too many people out there trying to make a buck by preying on the hopes of those caring for a loved one with Alzheimer’s or on the fears of those desperate to avoid the disorder.

I cannot judge Dr. Mercola’s motivation, but I do note that his site sells the products he espouses.

My second reaction is to check the information out.

This particular article makes so many claims, it will take some time to go through them all, but I think it may be worthwhile to do so.

The first two paragraphs of the article are absolutely 100% accurate.

There is no reference cited for the projection in paragraph three that Alzheimer’s will increase in prevalence from the current one in eight persons age 65 and over, to a state where one in four Americans will be affected. It is unclear whether we are now talking about one in four Americans age 65 and over, or just one in four Americans.

But put aside for the moment the fact that we don’t know exactly to whom the “one in four” refers. Whatever group is meant, this is a major increase.

But you have to wonder… How much of the increase is due simply to the increase in elderly people in the population? We are, thanks to our current excellent health care system, living longer, healthier lives than ever before. It was not that long ago that few adults lived long enough for the neurodegenerative diseases associated with aging to show themselves. One reason the incidence of Alzheimer’s is going up is that we are doing a better job of not dying from other causes. Scary as this projection is, it is unsubstantiated (no reference) and may be misrepresented… or not (we can’t tell since the wording is imprecise). So one probably should not give it much weight.

The fourth paragraph is accurate, but fails to mention that there is no way to objectively determine whether any particular regimen prevents Alzheimer’s, since we don’t really know what causes it and we cannot predict who is going to get it.

There are a few families in which Alzheimer’s is hereditary and caused by specific gene defects. (Don’t worry. If you were in one of these families, you’d know it—researchers would be knocking at your door.) People from these families are not included in clinical trials, since they would skew the data. Familial Alzheimer’s, as it is called, accounts for approximately 10% of all cases.  The other 90% of Alzheimer’s cases are sporadic, meaning the disease occurs for no apparent reason.

The next two paragraphs continue to imply that there is a known regimen that will decrease your risk of getting Alzheimer’s. But there isn’t. We do, however, know a few things about brain health and some of the suggestions later in the article are based on that information.

So thus far, the article is reasonably accurate, but does make some implications that could be misleading. Next time we’ll begin analyzing the specific recommendations one by one.

Until then…



Developing new drugs for Alzheimer’s Disease: Targeting misfolded proteins

The search for new drugs

When scientists search for new drugs, they begin by looking at the disease or disorder in question. If the cause of a disorder is known, research focuses on attempting to eliminate it. But if that doesn’t work, or if a scientist is studying a disease like Alzheimer’s, where the cause is not known, then she begins to look at the major problems or symptoms of the disease. Three of the major problems in Alzheimer’s disease are 1) synapses that don’t work properly, 2) neurons that lack the energy they need to function, and 3) misfolding of specific proteins.

Two weeks ago, I wrote about the synapses and drugs that directly affect synaptic transmission. To see that post, click here. Last week, the topic was the energy deficit in Alzheimer neurons, and the search for drugs that enhance mitochondrial function. You can read about that here.

Today, I want to begin talking about the misfolded proteins of Alzheimer’s disease. It’s a complicated topic, so we’re going to approach it bit by bit. First, we need some background information:

For proteins, folding properly is a big deal

When your cells make proteins, they connect protein subunits (called amino acids) together like beads on a string. There are twenty common subunits, each with a different 3-D shape. The subunits used and the order in which they are strung determines many of the traits of the protein made.

Now this is the part that is important to understand… The function of a protein depends on its three-dimensional shape.

When proteins are being made, there is an entire class of helper proteins (called chaperones) who have the important job of making sure the new proteins get folded into their proper functional shapes. (Yes, “who.” I fully intend to talk about proteins as if they were people. Grammarians will just have to deal with it.)

But proteins don’t always stay neatly folded. Changes in temperature, changes in acidity, even interactions with other molecules can cause proteins to change their shape.

If a protein unfolds completely and stays that way, it is essentially dead and cannot perform its function in the cell. (This is, quite literally, what happens when you cook an egg. Egg white is a protein called ovalbumin, and when it is unfolded, it goes from being clear and runny to being white and stiff.) Though we eat and digest many denatured proteins, allowing the subunits they are made of to be recycled, within the cell, proteins that are even partially unfolded are essentially useless.

Normally, unfolded or misfolded proteins are degraded and destroyed by the clean-up organelles of the cell.

In Alzheimer’s disease, misfolded proteins persist

However, in Alzheimer’s disease, beta-amyloid protein and the protein tau adopt abnormal misfolded shapes, and the cell is unable to degrade them properly.  Beta-amyloid is the main component of the senile plaques found in Alzheimer brain. Tau protein produces tangles inside the neurons.

Both beta-amyloid protein and tau protein are targeted by drug developers. In future posts, I’ll write about the approaches being used to fight their deposition in brain.

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If you’d prefer some lighter reading, try my Transitions blog.

Wishing you the best,


New Drugs for Alzheimer’s: The Energy Connection

Last Friday, I discussed drugs that treat the synaptic dysfunction of Alzheimer’s Disease (AD). This week we will look at drugs that aim to safeguard brain neurons by protecting their energy supply. These drugs affect the function of organelles within the cell called mitochondria.

If you remember mitochondria from past Biology classes, the phrase “powerhouse of the cell” may come to mind. The function of mitochondria is to produce ATP molecules, which the cell uses as a form of stored energy.

ATP stands for adenosine-tri-phosphate—basically an adenine nucleotide with three phosphate groups attached. The phosphate groups are highly positively charged. To push three positive phosphate groups together takes a lot of energy, because objects of the same charge repel one another. So energy is used to form the bonds holding ATP together, and can be released by breaking, or cleaving, the bond holding the third phosphate in place.

When neuronal mitochondria become less effective producers of ATP, neurons don’t have the energy they need for metabolism, repair, and signaling. If mitochondrial function is badly impaired, neurons die.

Looking for drugs that protect organelle function is a new approach to treating Alzheimer’s Disease, but it makes sense. Mitochondria dysfunction occurs early in AD and promotes synaptic damage as well as neurodegeneration. Furthermore, amyloid proteins can interact with the mitochondria to cause even more impairment in the brain.

When researchers began to study mitochondria in AD, they found that some drugs already in use (Donepezil and Memantine) helped preserve mitochondial structure and enhanced mitochondrial function. How much of their effectiveness in AD is due to mitochondrial protection and how much to receptor blockade is not yet clear.

One new drug that enhances mitochondrial function is currently being tested on AD patients. Thus far it appears that this drug, Latrepirdine, is effective and improves overall well-being in people with AD.

Related articles: Alzheimer’s Disease: physical changes in AD brain. Alzheimer’s Disease: biochemical changes in AD brain. Finding new drugs for the AD brain.