Though the tragic death of noted Alzheimer’s researcher Dr. Mark Smith has silenced the voice of one of the leading critics of the so-called amyloid theory, Smith’s Case Western Reserve University colleagues expect to carry on his work.
Smith died this week at 45 after a hit-and-run accident that sent shock waves throughout Case’s research community. He was dubbed a renegade researcher for the controversial and contrarian position he held on the cause of Alzheimer’s disease.
He challenged the idea — which at this point is somewhat conventional wisdom — that protein fragments called amyloid caused Alzheimer’s. (As an example of how dominant the theory of the amyloid-Alzheimer’s connection is, Cleveland Clinic named an imaging agent used to identify amyloid in brain scans as its 2011 medical innovation of the year.)
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Smith and his team took things a step further, theorizing that not only is it mistaken that amyloid causes Alzheimer’s, but the substance actually protects the brain, so blocking it may be dangerous. Thus far, clinical trials of amyloid-reducing drugs have failed, lending credence to Smith’s theory that the protein isn’t responsible for Alzheimer’s.
“He was the most articulate and powerful advocate for examining alternate hypotheses, and in almost all fields you need that gadfly,” said Dr. Robert Petersen, a Case researcher who knew Smith since the early 1990s. “You need that person sitting down, biting at you and making you think. It’s a rare person who has the fortitude to do that on a consistent basis.”
In the absence of such a strong agitator, it’s fair to wonder about the future of the hypotheses that Smith and his colleagues advanced. Don’t worry, according to Smith’s fellow Case researchers.
“In terms of the science, he was at the front as an advocate, but it wasn’t just one person,” Petersen said.
Smith worked closely with researchers Dr. Xiongwei Zhu and Dr. Hyoung-Gon Lee for years, having published about 200 research papers with Zhu and 100 with Lee, the researchers said. Another key collaborator, Dr. George Perry, moved on from Case to become dean of the College of Sciences at the University of Texas at San Antonio but still worked frequently with Smith, Zhu and Lee.
“We work as a group, and we publish as a group,” Lee said.
Smith’s death provides the opportunity for Zhu, Lee and Perry to take on more public roles in spreading the word of their doubts about amyloid theory, Petersen said.
Had Smith suffered the same tragedy years ago, development of the amyloid-challenging theory may have stalled, Zhu and Lee said. But because they both had so many years to work by Smith’s side and share in his knowledge, they’re confident that work will continue.
“With support from the university and community and our collaborators, we think we can carry on these studies,” Zhu said.
