Untangling Alzheimer's

Untangling Alzheimer's Disease

Initially, scientists thought Alzheimer’s was a simple, straightforward problem to solve.

plaque in Alzheimers brain

Most drugs tested in clinical trials are directed against amyloid that accumulates outside of neurons. A new model from Columbia scientists predicts that this site of amyloid accumulation is just the "smoke" and not the "fire." Read more: Drugs Can’t Stop Alzheimer’s. A New Model of the Disease Explains Why.

“We hoped that there would be one big mutation [that caused the disease] and everything would be fixed,” says Richard Mayeux, MD, the Gertrude H. Sergievsky Professor of Neurology, Psychiatry, and Epidemiology and chair of neurology at Columbia University Vagelos College of Physicians and Surgeons.

“But it’s not.”

Years of disappointing clinical trials have seen one drug after another fail to slow the disease.

“I think we’ve tried a lot of the obvious stuff and now we have to draw from many disparate fields to create a solution totally different from what we’ve tried before,” says Anthony Fitzpatrick, PhD, assistant professor of biochemistry & molecular biophysics and principal investigator at Columbia University’s Zuckerman Institute.

Columbia scientists are now becoming cautiously optimistic that a solution is within reach.

“The analogy used is the baseball playing field,” says Scott Small, MD, the Boris and Rose Katz Professor of Neurology and director of Columbia’s Alzheimer's Disease Research Center. 

Structure of an Alzheimers tau tangle solved with the help of cryo-electron microcopy

Columbia researchers are using cryo-electron microscopy to uncover the structure of the tau tangles seen in the brains of Alzheimer's patients. The structure may lead to drugs that can prevent tangle buildup. Read more: Alzheimer's Goes Under the Cryo-Electron Microscope.

“For a number of years, we were either in the wrong playing field or the lights were off.

“What’s clearly happened is that we’re now swinging in the right playing field. When will that home run–an effective intervention–be hit? Will it be one year, two years, three, five, 10? It’s hard to know, but I know it will be hit.”


This article was adapted from How Columbia University is Untangling Alzheimer's, first published on the Zuckerman Institute website.