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Study: Immune system may attack memory cells

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Study: Immune system may attack memory

cells

By Talan

Staff Writer

Posted August 20 2004

In animal research designed to

figure out why lupus patients have memory problems, scientists have discovered

that the immune system can send defensive antibody cells into the brain and

selectively kill memory cells.

" This is an important finding that could immediately lead to the

development of treatments to prevent mental impairment in people with

auto-immune disorders, " said Dr. Tracey, head of patient research at

North Shore-Long Island Jewish Research Institute in Manhasset. " The link

between cognition and immunity was unanticipated. "

Not only did the scientists show the immune system antibodies could get into

the brain and target glutamate-rich cells of the hippocampus, the seat of

learning and memory, but they showed the Alzheimer's drug Namenda

or memantine, could block this cell death in animals.

" It brings us a step closer to a rationale for clinical trials in

patients, " said Dr. Betty Diamond, an immunologist and rheumatologist at

the Albert Einstein College of Medicine in the Bronx.

The animal study, in the latest issue of the journal Immunity, was done in an

attempt to understand why so many people with lupus complain of memory

problems. Diamond carried out the study with her husband, Dr. Bruce Volpe, a

neurologist at New York Weill Cornell Medical Center in Manhattan.

Lupus is an auto-immune disorder that affects 500,000 to 1 million people in

the United States, mostly

women. The body's immune system turns on itself and makes specific antibodies

that attack the kidneys and other organs. Just a few decades ago, more than 50

percent of patients died within 10 years after diagnosis. Today,

immunosuppressive drugs are used to keep these immune cells from damaging

tissues, and the majority now live much longer.

However, many patients are now vulnerable to infections because of their

lowered immunity. As patients live longer, memory and learning problems are

becoming more common, Diamond said.

The animal studies allowed them to study how the immune culprits, so-called

anti-DNA antibodies and anti-nuclear antibodies, get into the brain and do

their damage. These antibodies roam the body and for the most part don't have

access to the brain, which is protected by the blood-brain barrier. But studies

have shown that the blood-brain barrier can temporarily open in response to

several things, including infection.

It is only when the blood-brain barrier is breached that the rogue antibodies

get through and head to the hippocampus, where they start killing the

glutamate-containing cells. Somehow, the auto-antibodies

cross-react with these glutamate receptors.

Glutamate is a neurotransmitter that excites cells into action to carry out a

specific job. Too much stimulation of these receptors causes cell death. The

result: The animals suffered the same cognitive, or thinking, problems as

patients do, Diamond said.

But when they gave the animals a dose of the Alzheimer's drug memantine, and then forced the blood brain barrier open,

the glutamate-rich hippocampus cells did not die. Memantine

filled the receptors so the autoantibodies couldn't

get inside the cells to do damage.

Diamond said it is important to conduct clinical trials before lupus patients

add yet another medicine to their treatment mix.

" We have to test whether it works the same way in people, " she said.

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