Research report on aging

I am at the American Association for the Advancement of Science meeting in Vancouver, Canada, sitting in on a session about aging. The first presentation provided an overview of Alzheimer’s disease, as well as some insights into one area of treatment-related research. There is one session dedicated completely to Alzheimer’s at this meeting, but it’s on Monday, the day I travel back to Ohio, so I will miss it. This is a giant meeting about all types of science, so I’m not surprised there aren’t more presentations about the disease here.

The presenter was Robert Vassar of Northwestern University. Because this session is partly about the societal effects of aging, he gave an overview. In case you are not familiar with the latest statistics: 5.4 million Americans currently have Alzheimer’s, and experts estimate that about 13 million Americans will have the disease by 2050. Currently, health care costs associated with Alzheimer’s stand at about $183 billion per year. If therapies that can alter the disease process aren’t discovered soon, Vassar said, Alzheimer’s “threatens to bankrupt our national economy.”

Vassar’s research concentrates on one of the enzymes that allows for the release of amyloid beta – little pieces of protein – in the brain. The presence of amyloid beta plaques in the brain is a hallmark of Alzheimer’s, and though no one knows for sure, it’s believed that these plaques contribute to the disease rather than form as a consequence of the disease. There are two known partner enzymes that allow for the release of these protein chunks, and Vassar is focused on beta secretase. The thought is that if one of these enzymes were prohibited from carrying out its function in the brain (releasing the protein pieces), the resulting reduction in free-floating amyloid beta in the brain could in turn prevent development of the disease. (There is also a school of thought that tau tangles cause Alzheimer’s, but Vassar advanced the theory that the toxic nature of amyloid beta plaques leads to the presence of tau tangles, which scientists now believe can transfer from one brain cell to another.)

As part of this pursuit, Vassar and colleagues genetically deleted this enzyme in a mouse model and, at first glance, these mice appeared to remain normal. They were still fertile. Their tissues also looked normal. This is important, because even when scientists find what appears to be a clear target for a new drug, they have to find out whether using a drug to delete that target from the body would have consequences far worse than fixing the disease.

When these mice were crossed with mice that were altered to develop amyloid beta plaques in their brains, the formerly diseased mice were rescued from the worst effects of those plaques: Their memory improved so much that they resembled normal mice. These findings were a “green light” to go forward with plans to eliminate the beta secretase enzyme as a treatment strategy.

But when Vassar took a closer look at the mice who lacked the enzyme, he discovered that they had a number of mild neurological problems – bad performance on memory tests concerning time and space, hyperactivity, a loss of myelin around their nerve cells and even seizures. Despite all this, they could still function pretty well. He and colleagues also looked at how their brain cells communicate with each other, and saw that they had some faulty wiring in a specific area of the brain.

Vassar didn’t call any of these findings a “red light,” but instead called them reasons to be cautious in moving forward with efforts to target this enzyme as a treatment option for Alzheimer’s. It is probable that the enzyme he is targeting has other functions that remain unknown. “We need more research to understand normal functions of drug targets because it’s critical for determining the success of future disease-modifying treatments and for minimizing side effects,” he said.

He also said that among the research efforts focused on treatments that target the amyloid plaques, the furthest along are compounds that bind to amyloid beta and help remove it from the brain. Other research groups also targeting the beta secretase enzyme as well as the gamma secretase enzyme, which has a similar function, have experimental drugs in clinical trials. He also talked about the recent Case Western Reserve University research that found that a skin cancer drug dramatically reduced amyloid beta plaques in the brains of mice; the drug activates a set of genes to improve the clearance of the protein pieces away.

After the presentation, I thanked Dr. Vassar for doing this work. I wish I could personally thank all researchers who care about this population enough to devote their careers to the science behind the disease.

2 comments so far

  1. Sayte Holland McComb on

    I am so glad that you have this opportunity every year to really get inside what is going on in research + I thank you for sharing your experience and what you learn. One of my best friends mother is in a facility, she is far-far more progressed than your mom, plus her grandmother died from the disease. I would assume that this increases her liklihood of developing it also and it is very unsettling to me to say the very least. I wish you a good trip & I am sorry that OSU doesn’t throw in a week for you all to travel & take in the sites there. Give my big brother a smile from me.

  2. momsbrain on

    Hi, Sayte! I am inspired to be just a little bit journalistic here, surrounded by media covering the meeting. I have another post to write about the rest of my session. As for higher risk for children/grandchildren of current patients – I think it’s safe to say that is not established, except in certain cases of early onset Alzheimer’s. I live such a different life than my mom did – if I am at higher risk genetically, I am hoping my lifestyle differences will have a preventive benefit or at least mean it will arrive later in my life than it did in Mom’s and something else can get me instead. Of course, none of the preventive stuff is really proven, either, but the behaviors don’t hurt. I gave Earle your regards!

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