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Researcher eager to solve the Alzheimer's puzzle

Santa Cruz Sentinel (CA)


April 18--FELTON -- When Daniel Zwilling was 21, his grandfather, a surgeon, had a stroke, and that set Zwilling on a course to learn more about the brain and why it sometimes does not work properly.

Today, Zwilling, 39, a native of Germany, is an up-and-coming researcher at the Gladstone Institute of Neurological Disease in San Francisco, which makes him a colleague of 2012 Nobel Prize winner Shinya Yamanaka for his research on reprogramming sick cells.

Zwilling spoke Wednesday about recent developments in research on Alzheimer's, a disease that affects more than 5 million Americans and for which there is no cure.

Close to 200 people attended the conference sponsored by the Alzheimer's Association and hosted by the Mount Hermon Conference Center, according to Dale Thielges of the Alzheimer's Association.

With care for people with Alzheimer's costing $172 billion in 2010, Zwilling said, "We need to try to prevent the disease to minimize these costs."

Much of what we know about memory comes from research on Henry Molaison, who in his 20s had part of his brain, the hippocampus, surgically removed to cure his epilepsy.

"It cured the epilepsy but came at a high price," Zwilling said, explaining that without the hippocampus, Molaison could not remember anything after the surgery.

With Alzheimer's, the brain shrinks and there is atrophy in the hippocampus, which can be seen in an MRI.

Zwilling described the ApoE protein, which helps repair damage to brain cells, and how one version, ApoE3,is "good" and another, ApoE4, is "bad" and associated with Alzheimer's. Both are produced by genes, but neither is recessive.

Another variant, the ApoE2 protein, protects against Alzheimer's.

About one-fourth of the population has the ApoE4 protein; having one ApoE4 genotype doubles the risk for Alzheimer's for men and quadruples the risk for women.

Having two ApoE4 genotypes increases the risk 10-fold to 12-fold, but "(it) doesn't mean for sure you will get Alzheimer's," Zwilling said.

At Gladstone, researchers are asking: Can we find a drug that converts ApoE4 into a molecule like ApoE3?

Dozens of drugs are in clinical trials, but "so far, nothing has translated into effective cures," Zwilling said, noting many have failed in stage 2 and 3 because of toxic side effects.

For now, he said, the ways to reduce the risk include exercise, a heart-healthy diet, brain stimulation, nutrition, vitamins, antioxidants and Omega 3 fatty acids, socializing and red wine, one or two glasses daily.

Asked what appears promising, Zwilling said, "I like the idea of using antidotes that go into the brain."

One woman suspects medications are causing her sister's memory loss since an MRI showed her sister's brain has no sign of Alzheimer's.

The Food and Drug Administration has warned statins, such as Lipitor, prescribed to reduce cholesterol, could increase memory loss and confusion.

"I appreciate the point about misdiagnosis of Alzheimer's," said Dr. Elizabeth Endsley of the Alzheimer's Association. "We do have to be careful."

Follow Sentinel reporter Jondi Gumz on Twitter at


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