Monday, May 25, 2009

Are We Moving Closer to Determining the Cause and Cure of Alzheimer’s Disease?

Several aspects of Alzheimer’s Disease have not been well understood. Why do Alzheimer’s patients have days of lucidity, but for unknown reasons slip back to the disease?  Earlier I reported that an Antihistamine drug was taken off the market because it blocked the production of an enzyme that destroys excess proteins in the muscle. That observation combined with the mice study that showed that getting rid of soluble excess protein in the brain stopped the symptoms of Alzheimer's seemed to be a good approach in Alzheimer's Disease research!  Mice studies show that the introduction of an enzyme that destroys excess protein in the mice’s brain made the Alzheimer’s mice normal again! It could be that excess protein in the brain leads to poorer synaptic connections and plaque. (Harper's Magazine, Last page, probably 2007 or 2008.

This approach to curing Alzheimer’s was hinted at by a Harvard Medical School researcher on PBS. He  said during the discussion period that he thinks a new area of study should include the effect of synapse connection and disconnection in explaining the symptoms of Alzheimer's patients moments of lucidity. Perhaps the excess proteins in the brain which leads to plaque and eventual death could interfere with the connection of the synapses causing difficulty in the brain's ability to remember or store memory.

From  Author, Melody Petersen, a former award winning reporter for the New York Times in her book "Our Daily Meds," Pages 36-37 “By early 2006, Detrol (bladder control drug) was selling at a rate that would bring Pfizer an expected one billion dollars for the year ... Neurologists at the University of Florida studies the women's (dementia) cases. They questioned whether the diagnosis of Alzheimer's disease had been too swift. They went over the clues and began to understand what connected the two women: they both had lost their memories after beginning to take Detrol. Both women regained much of their memories after they stopped taking the pills. ... (Seniors take about an average of 15 drugs daily. Jim)

Both bladder drugs have what doctors call anticholinergic, which means they block the action of acetylcholine, a neurotransmitter. Nerve cells release neurotransmitters to send signals to neighboring cells. The anticholinergic medicines block some of these signals. Many drugs, including some used to treat allergies, blood pressure, convulsions, depression, Parkinson's disease, and psychosis, have been found to have anticholinergic effects. So many medicines have anticholinergic effects that some people may be taking two or more of these drugs at the same time. 

Scientists have found what they believe is physical evidence of harm from these anticholinergic drugs in the brain. In 2003 British researchers studied the brains of patients who had died from Parkinson's disease. They found that the brains of the patients who had taken anticholinergic drugs for two years or longer had more than twice the level of abnormal clumps of amyloid plaque and tangled bundles of fibers as those who had not taken the drugs or had taken them for a short time. Such plaque and tangled fibers in the brain are considered the hallmarks of Alzheimer's disease. 

Doctors have found that this medication-induced dementia often reverses if it is found and the patient stops taking the offending drug. But how many people never learn that it was their medicine that took their minds away? ...” Melody Peterson “Our Daily Meds.”

Benedict Carey May New York Times May 21, 2009 “... So far, scientists here have found little evidence that diet or exercise affects the risk of dementia in people over 90. But some researchers argue that mental engagement — doing crossword puzzles, reading books — may delay the arrival of symptoms. And social connections, including interaction with friends, may be very important, some suspect. In isolation, a healthy human mind can go blank and quickly become disoriented, psychologists have found.

“There is quite a bit of evidence now suggesting that the more people you have contact with, in your own home or outside, the better you do” mentally and physically, Dr. Kawas said. “Interacting with people regularly, even strangers, uses easily as much brain power as doing puzzles, and it wouldn’t surprise me if this is what it’s all about.” And bridge, she added, provides both kinds of stimulation.  ...” 

Tau Proteins in the Brain Go Out of Control and Form Tangles and Plaque Primary Causes of Alzheimer's Disease ScienceDaily (May 23, 2009) — A discovery made by researchers at McGill University and the affiliated Lady Davis Research Institute for Medical Research at Montreal's Jewish General Hospital offers new hope for the early diagnosis and treatment of Alzheimer's disease.

In a study published in the Journal of Biological Chemistry on May 15, Dr. Hemant Paudel, his PhD student Dong Han and postdoctoral fellows Hamid Qureshi and Yifan Lu, report that the addition of a single phosphate to an amino acid in a key brain protein is a principal cause of Alzheimer's. Identifying this phosphate, one of up to two-dozen such molecules, could make earlier diagnosis of Alzheimer's possible and might, in the longer term, lead to the development of drugs to block its onset.

The crucial protein, called a tau protein, is a normal part of the brain and central nervous system. But in Alzheimer's patients, tau proteins go out of control and form tangles that, along with senile plaques, are the primary cause of the degenerative disease. ... McGill University (2009, May 23). Alzheimer's Discovery Could Bring Early Diagnosis, Treatment Closer. ScienceDaily. Retrieved May 23, 2009, from 

Agents That Speed Up Destruction Of Proteins Linked To Alzheimer's Discovered

ScienceDaily (Apr. 22, 2009) — Taking a new approach to the treatment and prevention of Alzheimer's disease, a research team led by investigators at the Mayo Clinic campus in Florida has shown that druglike compounds can speed up destruction of the amyloid beta (A-beta) proteins that form plaque in the brains of patients with the disorder.

Researchers say their study, published in the April 22 online issue of PLoS One, demonstrates that this strategy is a viable and exciting alternative to the approach most drug designers have taken to date.

"Historically, a lot of effort has been made at stopping initial production of A-beta in order to halt development of Alzheimer's disease, but we are interested in what happens to A-beta after it is produced," says the study's lead researcher, Malcolm Leissring, Ph.D., from Mayo's Department of Neuroscience.

The researchers found two chemicals that could speed up activity of a molecule, insulin-degrading enzyme (IDE), which helps chew up A-beta proteins produced in the brain.

In laboratory experiments, they found that one agent, dubbed Ia1, increased the activity of IDE by about 700 percent, while the second compound, Ia2, increased it by almost 400 percent. ... Mayo Clinic (2009, April 22). Agents That Speed Up Destruction Of Proteins Linked To Alzheimer's Discovered. ScienceDaily. Retrieved April 22, 2009, from /releases/2009/04/090421205319.htm

Jim Kawakami

May 26, 2009

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