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Tuesday, January 2, 2001, 12:00 p.m. EDT
Environmental Health Institute Scientists Begin to Unravel Cause of Blocked Memory in Alzheimer's
Researchers at the National Institute of Environmental Health Sciences (http://www.niehs.nih.gov) have found that a protein found in patients with Alzheimer's disease can disrupt brain signals and therefore may contribute to the memory losses of Alzheimer's disease, the scientists reported today in the Journal of Neuroscience (http://www.jneurosci.org/) , 2001, Vol. 21, RC 120, pp. 1-5.
According to the report, the characteristic plaques seen by scientists and physicians in the brains of Alzheimer's patients may not be the result of the disease but a cause. (At autopsy, these characteristic plaques -- first noted in 1906 -- are used to confirm Alzheimer's.)
The NIEHS scientists said they had demonstrated in rat brain that the major protein of these plaques binds to a receptor in the brain, thus blocking the signals, or currents, that are thought to be involved in learning and memory. The protein is called Beta-amyloid peptide and is found in the brains and plaques of humans, as well as animals.
Many researchers have speculated that the protein had such a memory-blocking role but, according to the authors, this work for the first time establishes this functional link between the plaques seen at autopsy and the failure in brain functioning.
The senior NIEHS scientist on the study, Jerrel L. Yakel, Ph.D. (http://www.niehs.nih.gov/research/atniehs/labs/ln/icp/index.cfm), said that better drug therapies could result from finding chemicals that prevent the chemical binding and thus keep the brain signals flowing. "Knowing how the disease process works," Dr. Yakel said, "makes it more likely that medical science can find ways to slow, halt or even reverse the process."
Dr. Yakel, Diana L. Pettitt, Ph.D., and Zuoyi Shao, Ph.D., showed that the Beta-amyloid peptide blocks the function of a key signaling receptor, the nicotinic acetylcholine receptor, in the hippocampus -- the seat of memory, motivation and emotion in the brain. For the text of the scientific report, see the full Yakel/Pettit/Shao report at http://www.jneurosci.org/rapidcomm.shtml.
Alzheimer's is the most common form of dementia -- a medical condition that disrupts the way the brain works -- in older people. It is characterized by confusion, profound forgetfulness and, often, anger. Seldom diagnosed a few decades ago, the disease appears to be increasing as the U.S. population ages and currently affects an estimated four million Americans.
In rare cases, the disease begins to develop before age 50 but most cases develop after 65. Alzheimer's Disease, or AD, is named for the German physician Alois Alzheimer. In 1906, he noticed abnormal clumps (now called senile or neuritic plaques) and tangled bundles of fibers in the brain tissue of a woman who had died of a then-unusual mental illness. These plaques and tangles in the brain are now considered to be hallmarks of AD.
Alzheimer's may begin as mild forgetfulness about recent events, activities, and the names of people and things. Simple math may become hard.
As the disease progresses, people may forget how to do such tasks as combing their hair or brushing their teeth. They may no longer think clearly: Speaking, understanding, reading and writing become difficult. Patients may become anxious or aggressive as the disease continues to progress, and they often wander from home. AD patients eventually need total care.
Because such problems may result from other conditions as well, doctors can only make a probable diagnosis of Alzheimer's - though in specialized centers this is correct 80 to 90 percent of the time. Since it is risky to remove brain tissue from a live person, doctors cannot confirm AD with total accuracy unless they do an autopsy after death to determine if there are plaques and tangles in the brain.
Several drugs have been approved for temporarily relieving some symptoms of Alzheimer's but there is no cure or drug that can arrest the disease.
The National Institute of Environmental Health Sciences is one of the institutes of the National Institutes of Health (http://www.nih.gov) . NIEHS' headquarters and laboratory, where the Yakel-Pettit-Shao team work, are in Research Triangle Park (http://www.rtp.org) , between Raleigh (http://www.raleigh-nc.org) and Durham (http://www.durham-nc.com) , N.C.