Uncovering The Mysteries of Alzheimer's Disease
By Bonnie Prescott
Beth Israel Deaconess Medical Center Staff
Alzheimer’s disease might be described as a “tangled mind.” The widespread form of dementia – currently affecting more than 5 million individuals in the U.S. alone – leaves its victims confused, scared and robbed of memory and the ability to function.
Ironically, when scientists look at tissue from an Alzheimer’s patient under the microscope, they see actual “tangles”; bits of protein that have become twisted and knotted. They also see misshapen protein clumps known as “plaques.”
“More than a century ago, in 1906, the German doctor Alois Alzheimer first observed an abundance of these ‘plaques’ and ‘tangles’ in the brains of Alzheimer’s patients,” explains Dr. Kun Ping Lu, a cell biologist at Beth Israel Deaconess Medical Center who studies cancer and Alzheimer’s disease. “Throughout the years, intensive studies have been done to find out what was causing these lesions to develop, what chemical changes were leading to these misshapen lesions.”
Both of these brain lesions are caused by an abnormal buildup of proteins or protein fragments. The tangles are made up of a protein called tau and the plaques are composed of protein fragments, referred to as APP.
One area that scientists are investigating revolves around an enzyme called Pin1, which was first discovered by Dr. Lu in 1995. Since then, Dr. Lu and his colleagues have made several key observations regarding the role that Pin1 might play in the development of Alzheimer’s disease.
In test tube experiments, Dr. Lu and his team administered Pin1 to misshapen tau tangles found in Alzheimer’s disease. They learned that the enzyme successfully “untangled” the knots so that the tau protein would function properly. Furthermore, by looking at changes in levels of the Pin1 protein in the brains of patients who had had Alzheimer’s disease, they learned that Pin1 is especially low in those neurons that are most vulnerable to degeneration in Alzheimer’s. Finally, to examine the significance of reduced Pin1 function in the development of Alzheimer’s, they created an animal model in which Pin1 had been removed. The result was that the neurons in the brain collapsed under the weight of the resulting clumps and tangles.
Later experiments showed that Pin1 had a similar effect on the plaques that had built up in the brains of Alzheimer’s patients, restoring APP to its normal function.
“Pin1 is like the oil in a car engine,” explains Dr. Lu. “You need oil to keep it running smoothly; without it, things begin to break down. If you don’t have Pin1, then the proteins become misshapen and turn into plaques or tangles.”
Dr. Lu is currently continuing his investigations of Pin1, trying to determine whether reduced Pin1 levels in the blood can be used to predict individuals at increased risk of developing Alzheimer’s disease. Pin1 is also being looked as a possible target for the development of drugs to treat Alzheimer’s.
“There is a lot more work to be done, but in our work so far, Pin1 appears to play an important role in Alzheimer’s disease,” he says.
Above content provided by Beth Israel Deaconess Medical Center.
For advice about your medical care, consult your doctor.
Posted December 2008
Beth Israel Deaconess Medical Center Staff
Alzheimer’s disease might be described as a “tangled mind.” The widespread form of dementia – currently affecting more than 5 million individuals in the U.S. alone – leaves its victims confused, scared and robbed of memory and the ability to function.
Ironically, when scientists look at tissue from an Alzheimer’s patient under the microscope, they see actual “tangles”; bits of protein that have become twisted and knotted. They also see misshapen protein clumps known as “plaques.”
“More than a century ago, in 1906, the German doctor Alois Alzheimer first observed an abundance of these ‘plaques’ and ‘tangles’ in the brains of Alzheimer’s patients,” explains Dr. Kun Ping Lu, a cell biologist at Beth Israel Deaconess Medical Center who studies cancer and Alzheimer’s disease. “Throughout the years, intensive studies have been done to find out what was causing these lesions to develop, what chemical changes were leading to these misshapen lesions.”
Both of these brain lesions are caused by an abnormal buildup of proteins or protein fragments. The tangles are made up of a protein called tau and the plaques are composed of protein fragments, referred to as APP.
One area that scientists are investigating revolves around an enzyme called Pin1, which was first discovered by Dr. Lu in 1995. Since then, Dr. Lu and his colleagues have made several key observations regarding the role that Pin1 might play in the development of Alzheimer’s disease.
In test tube experiments, Dr. Lu and his team administered Pin1 to misshapen tau tangles found in Alzheimer’s disease. They learned that the enzyme successfully “untangled” the knots so that the tau protein would function properly. Furthermore, by looking at changes in levels of the Pin1 protein in the brains of patients who had had Alzheimer’s disease, they learned that Pin1 is especially low in those neurons that are most vulnerable to degeneration in Alzheimer’s. Finally, to examine the significance of reduced Pin1 function in the development of Alzheimer’s, they created an animal model in which Pin1 had been removed. The result was that the neurons in the brain collapsed under the weight of the resulting clumps and tangles.
Later experiments showed that Pin1 had a similar effect on the plaques that had built up in the brains of Alzheimer’s patients, restoring APP to its normal function.
“Pin1 is like the oil in a car engine,” explains Dr. Lu. “You need oil to keep it running smoothly; without it, things begin to break down. If you don’t have Pin1, then the proteins become misshapen and turn into plaques or tangles.”
Dr. Lu is currently continuing his investigations of Pin1, trying to determine whether reduced Pin1 levels in the blood can be used to predict individuals at increased risk of developing Alzheimer’s disease. Pin1 is also being looked as a possible target for the development of drugs to treat Alzheimer’s.
“There is a lot more work to be done, but in our work so far, Pin1 appears to play an important role in Alzheimer’s disease,” he says.
Above content provided by Beth Israel Deaconess Medical Center.
For advice about your medical care, consult your doctor.
Posted December 2008
