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Breakthroughs in battling and healing cognitive loss

Stanford Medicine researchers are investigating new tactics to overcome cognitive loss, including that which occurs in Alzheimer's disease.

For years scientists focused on fighting amyloids -- those damaging plaques that accumulate in the brain -- as the key to an Alzheimer's therapy. But neurologist Frank Longo, MD, PhD, always suspected there was more to the disease and that it would have to be attacked from many different angles.

"I think that with Alzheimer's and some of these other degenerative diseases, there are multiple forces that promote degeneration," said Longo, professor and chair of neurology at Stanford Medicine. "We wanted to create a therapy that could address multiple mechanisms at one time."

After 20 years of research, he's found a molecule, called C-31, that does just that. In animal studies, Longo and his colleagues found that the molecule had many beneficial effects in combatting the brain disease. Scientists in Europe recently tested it in 242 Alzheimer's patients and are now analyzing the results.

As I report in the latest issue of Stanford Medicine magazine, it's just one of the approaches scientists are pursuing to help restore cognitive function in Alzheimer's patients.

Understanding cognitive decline

Longo's colleague, Michael Greicius, MD, believes the answer to Alzheimer's lies in our genes. In his work with patients, he says it's become clear that some individuals carry a gene that naturally protects them from the disease. He's assembled a collection of sequenced genomes from more than 500 people with and without Alzheimer's in the search for a genetic variant that could confer this protection. Once that gene is identified, it could point the way to treatment.

"The idea would be to try to find drug targets in those molecular pathways -- mimic what these people have in their natural genomes," says Greicius, the Iqbal Farrukh and Asad Jamal Professor.

Inflammation in the brain also has long been considered a contributor to the cognitive decline associated with Alzheimer's. But scientists have never understood what drives this process.

Katrin Andreasson, MD, a professor of neurology and neurological sciences, recently identified a possible mechanism. She studied immune cells in the brain, known as microglia, in both older and younger people and identified a cascade of events that promoted a hyper-inflammatory environment in the brains of older adults. Mostly importantly, she found a way to interfere with the damaging process. She hopes the research will lead to a method to quell brain inflammation and help prevent the cognitive decline of Alzheimer's.

"If we could somehow change our microglia so they are behaving in a healthier way, that might go a long way toward slowing down the process of Alzheimer's disease," she said.

The full issue of Stanford Medicine magazine, "The most mysterious organ: Unlocking the secrets of the brain" can be found here.

Illustration by Harry Campbell

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