Cell Defect May Prove to Be Clue to Alzheimer’s

An apparent defect in cell structure that leaves certain proteins unable to withstand heat may be a clue to the cause of Alzheimer’s disease, a research team reported.

Scientists at the Veterans Administration Medical Center and the UCLA School of Medicine say a problem in cellular microtubules, the structural proteins responsible for cell movement, may impair a cell’s response to heat.

“The cells we’re studying are peripheral white blood cells, which are taken from an arm vein while drawing a blood sample,” researcher Dr. Lissy F. Jarvik said.

The white blood cells under study in the project are the leukocytes that come to the body’s defense in the event of exposure to bacteria, viruses, fungi or chemical toxins.

“We knew at the outset that these cells like to migrate to the warmest parts of the body,” she said, adding that they usually seem to know how to move away when things get too hot.

“Starting with below-normal body temperature, to temperatures where people develop very high fevers at about 105 to 106 degrees Fahrenheit, these cells in Alzheimer’s patients would commit heat suicide,” she said.

“They like it where it’s warm, but they don’t like to be cooked.”

Jarvik said the microtubules of people afflicted with the incurable brain disease apparently lose their ability to migrate by colliding with each other and coagulating.

“The cells, like Alzheimer’s patients, are disoriented,” she said.

Jarvik noted that microtubules are important because, in addition to helping cells move in response to such stimuli as heat or toxins, they also form the skeleton that holds a cell together.

Scientists have found that it is the microtubules that also form the spindle fibers that pull the chromosomes apart during cell division.

Just what causes the microtubules to go awry is the question that Jarvik and her research team are trying to answer.

“You need an intact microtubule system for cells to be able to migrate toward a goal,” she said. “We suspect the defect is in the microtubule system itself.

“This is only a suspicion and we have no hard evidence, but there is a certain amount of circumstantial evidence to support the possibility that the defect is in the microtubule system.”

Blood Samples Tested

As part of the study, Jarvik and her team took blood samples from 12 healthy volunteers ranging between 21 and 74.

To the test tubes of blood samples researchers added colchicine, an alkaline chemical known to impair microtubules. Results showed the colchicine disrupted the cells’ response to heat much in the same way they were impaired in Alzheimer’s patients.

Jarvik said a study conducted at the University of Minnesota 10 years ago first suggested a microtubule defect in Alzheimer’s disease.

That study also found a high frequency of people with Down’s syndrome among the relatives of patients with Alzheimer’s disease, she said.

Link to Down’s Syndrome

“There’s also another link with Down’s syndrome,” Jarvik explained. “Those people with Down’s syndrome who live to be about 35 or 40 years old almost invariably show Alzheimer’s changes in the brain.”

Alzheimer’s disease, which is characterized by progressive memory loss, affects an estimated 2.5 million Americans, manifesting most often in people over 65 but sometimes seen in middle-aged people.

In the worst cases, victims suffer seizures and almost all Alzheimer’s patients lose the ability to recognize close friends and family.