Archive for October, 2010

Alzheimer’s Disease Vaccine

One thing that I’m hoping for more than anything else is that a vaccine be developed for Alzheimer’s disease (AD). Wouldn’t it be great if we could stop our brains developing anything worse than an occasional senior moment? A couple of weeks ago, it was reported that researchers at  UT Southwestern Medical Center, after seven years, have created an experimental vaccine against beta-amyloid, the small protein that forms plaques in the brain and is believed to contribute to the development of Alzheimer’s.

This new experimental vaccine stimulated more than 10 times as many antibodies that bind to and eliminate beta-amyloid as compared to similar so-called DNA vaccines that the UT Southwestern researchers tested in an animal study. There are several studies that have to be done including:

  • safety of the vaccine and
  • whether it protects the mental function in animals.

According to Dr. Roger Rosenberg, director of the Alzheimer’s Disease Center at UT Southwestern and senior author of the study,
“The antibody is specific; it binds to plaque in the brain. It doesn’t bind to brain tissue that does not contain plaque. “This approach shows promise in generating enough antibodies to be useful clinically in treating patients.”

There was another vaccine tested a couple of years ago from the University of Southampton where British researchers gave 64 patients with moderate Alzheimer’s disease an experimental vaccine designed to eliminate plaque from their brains. Some patients were followed for up to six years.

Autopsies on seven patients who died of Alzheimer’s during the study showed that nearly all of the sticky beta-amyloid protein thought to be dangerous had been removed. But all patients still had severe dementia. So that was a disappointment. It will take a long time just to figure out what they need to target.

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Last week Reuters reported that international experts on Alzheimer’s disease (AD) are recommending that a new criteria for diagnosing Alzheimer’s should be used considering the recent scientific discoveries which includes the use of biomarkers (biological signals) which can determine if a person is at risk for developing the disease well before there are any symptoms. Hence, even as many as 10 years before any symptoms begin to show, it would be best to intervene. Recent studies have shown that brain scans, spinal fluid analyses, and other tests can possibly predict who will develop AD. With this knowledge, researchers and pharmaceutical companies can develop new drugs.

According to, the new criteria for diagnosing Alzheimer’s is much more accurate. It requires:

  • An early and significant episodic memory impairment
  • Gradual and progressive change of memory for more than 6 months
  • Objective evidence of recall memory that does not improve or does not normalize with adequate cueing or recognition testing

PLUS one or more of the following supportive features (the new early markers for increasing the specificity of a patient having AD):

  • Medial temporal atrophy on MRI
  • Abnormal spinal fluid concentrations of (1) amyloid, (2) total tau or (3) phospho-tau
  • Specific patterns of PET scanning producing hypometabolism of bitemporal parietal regions or Pittsburgh compound B
  • Proven AD autosomal dominant mutation within the immediate family

The criteria currently being used was adopted in 1984. In light of what the current research is showing, we are headed in the right direction to try to intervene as early as possible.

A new gene called MTHFD1L has been discovered by a team of researchers led by Margaret Pericak-Vance, Ph.D., director of the John P. Hussman Institute for Human Genomics (HIHG) at the University of Miami Miller School of Medicine. It appears to increase the risk of late-onset Alzheimer’s disease (AD) which accounts for 95% of Alzheimer’s cases. This gene might explain about 5 percent of the inherited AD. The study found that individuals with a particular variation in the gene MTHFD1L may be almost twice as likely to develop AD as those people without the variation.

So far, we believe that:

  • 60 to 80% of Alzheimer’s disease is attributable to genetic and environmental factors
  • 40% of that genetic effect is attributable to the ApoE4 variant

The importance of this study is that high levels of homocysteine are a strong risk factor for late-onset Alzheimer’s disease and the MTHFD1L gene is associated with the metabolism of folate and the raised homocysteine level. Look for foods rich in folate to increase your homocysteine level. Click here for suggestions. If you go for a physical on a regular basis, be sure to have your doctor include the homocysteine test in your blood work.

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In my last post, I talked about the possible shift in the cause of Alzheimer’s disease (AD) from sticky plaques to free-floating clumps of amyloid beta protein (oligomers). It’s possible that the sticky plaques may actually be protecting the toxic clumps and not the cause as was previously thought. Sam Gandy, MD, of the Alzheimer’s Disease Research Center at Mount Sinai School of Medicine in New York, has been working with specially engineered mice with AD where he found clumps of oligomers in their brains and no plaques.

According to Rudolph Tanzi, Ph.D., Director, Genetics and Aging Research Unit at the Massachusetts General Hospital, oligomers “should be enemy number one.” As the body ages, too many of these protein clumps create a damaging buildup in the brain and the brain may try to remove the offending oligomers by forming plaques.

Tanzi calls the plaques “brain pearls” and likens them to an oyster forming a pearl around a grain of sand to protect itself. Plaques may serve as traps for the oligomers that are attacking the brain. Some people who never have dementia have brains that are inundated with plaques and their brains may be been exceptionally good at converting the “sand” into “pearls.”

Several drugs are in the early stages of development aimed at the oligomers, with the emphasis on early. So this is the direction that research may be heading. A new drug bapineuzumab recently introduced to reduce plaque in the brain did not show any improvement in the subjects.

But it’s not a simple situation. According to Andrew Dillin, Ph.D., of the Salk Institute for Biological Studies, “I think plaques are a sign that your brain was trying to do something very beneficial for itself in the last stages of the disease. If you go in and take these plaques apart, you’re going to make oligomers, and that could actually be worse.”

We will anxiously wait to see what kinds of new medication are developed and how well they take care of the oligomers.

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