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Monday, Feb. 20, 2012

New leads emerge in battle against Alzheimer's


NEW YORK — Dementia is a general term that describes the decline in mental activity severe enough to interfere with daily activities. Of several types of dementia, Alzheimer's disease is the most common type, accounting for an estimated 60 to 80 percent of cases.

Although some medicines are palliative, none cures the disease. Fortunately a recent discovery may change the outlook for treatment and eventually lead to a cure.

It is estimated that 5.4 million Americans live with Alzheimer's today. Their care involves approximately 15 million people at an annual cost of $183 million. While deaths by HIV/AIDS, stroke and heart disease have diminished in the past several years, deaths due to Alzheimer's have steadily increased. Every 69 seconds, somebody in the U.S. develops the disease.

When, in 1901, Dr. Aloysius "Alois" Alzheimer, a German Psychiatrist and neuropathologist observed some unusual behavioral symptoms by Auguste Deter, a patient at the Frankfurt Asylum, he didn't realize that he would give his name to a devastating disease. Until he died in 1906, Mrs. Deter was Dr. Alzheimer's obsession. He could not forget the behavioral changes she exhibited, such as disorientation, confusion and impaired judgment.

Soon after Mrs. Deter's death, and with the help of two Italian physicians, Dr. Alzheimer used staining techniques to identify two crucial substances in the brains of people affected by Alzheimer's: abnormal clumps of protein fragments called beta-amyloid plaque, and disordered neurofibrillary tangles (twisted fibers composed largely of the tau protein, which build up inside nerve cells). These are two of the main features of the disease.

On Nov. 3, 1906, in a speech before medical colleagues, Dr. Alzheimer for the first time presented the symptoms and the pathology of the disease. A critical chapter had opened in the search to understand it. Regrettably his contribution to the study of Alzheimer's disease stopped in December 1915, when he fell ill on his way to the University of Breslau, Silesia, where he had been professor of psychiatry.

The high levels of beta-amyloid plaque and neurofibrillary tangles make it hard for the brain cells to communicate with each other. Although both substances are hallmarks of the disease, there is no agreement among scientists that they are a byproduct or if they cause the disease. The cells of the hippocampus, which is the center of learning and memory, are the first to be damaged. That's why memory loss is one of the first symptoms of Alzheimer's.

Fortunately, there has been steady progress since Alzheimer's original studies. A recent finding has considerably raised expectations for a cure. A group of researchers at Case Western Reserve University, Ohio, found that a cancer drug they have been testing in mice destroys the plaque found in the brains of people affected with Alzheimer's. Although many drugs that are successful in mice fail to work when tried on people, this finding gives reason for optimism.

Normally beta-amyloid is removed in the human body by a substance called apolipoprotein E, or ApoE. However, people have many different versions of this protein, one of which, ApoE4, is one of the biggest risk factors for developing Alzheimer's. Using a drug called bexarotene, the scientists were able to reduce the levels of beta-amyloid in mice.

After a single dose, the levels of beta-amyloid in the brain were rapidly lowered within six hours, and a 25 percent reduction was sustained for 70 hours. In older mice with more established beta-amyloid plaque, after seven days of treatment, the amount of plaque was reduced to a half.

What makes this experiment particularly interesting is that, after treatment, the mice showed improvements in brain function, nest building, maze performance and remembering electrical shocks.

One researcher, however, cautioned that although the study had been particularly rewarding and offered great promise, the drug had been tested in only "three mouse models" simulating early stages of the disease but are not Alzheimer's.

For a disease like this, which has caused so much damage and concern over the years, even these preliminary news are already good news.

Dr. Cesar Chelala is an international public health consultant.


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