Highlights from the panel on Alzheimer's research

Oscar Lopez, MD, (foreground) and Bill Klunk, MD (left)One of the most striking features of Alzheimer’s disease, according to Oscar Lopez, MD, is that “it’s the same in all populations. No matter where you go, the prevalence and the incidence is exactly the same.” 

This is the case even though one of the most important known risk factors for Alzheimer’s – carrying the e4 version of the APOE gene – varies by region, Lopez said.  He cites Finland and Spain as examples, where 20 percent and 9 percent of people, respectively, carry this genetic marker. (Not all people who have the APOE e4 allele will develop the disease.) Noted Lopez, “There are many things that we don’t understand.”

Lopez, who directs the Alzheimer Disease Research Center, was a panelist on critical issues and controversies in dementia research at Brain Day 2017. Moderated by Nathan Urban, PhD, Associate Director of the Brain Institute, the panel included Jeff Brodsky, PhD, Avinoff Chair of Biological Sciences and director of the new Center for Protein Conformational Diseases, and Jeff Brodsky, PhD, (foreground) and Chester Mathis, PhD, (left)Amantha Thathiah, PhD, assistant professor of neurobiology, Chet Mathis, PhD, Distinguished Professor of Radiology and UPMC Endowed Chair of PET Research, and Bill Klunk, MD, Distinguished Professor of Psychiatry and Neurology and Levidow-Pittsburgh Foundation Chair in Alzheimer's Disease and Dementia Disorders.  In a keynote address, Klunk spoke about how he and Mathis developed imaging techniques that detect abnormally high levels of amyloid beta, or a-beta, protein in the brains of people who later have developed the memory loss and cognitive decline seen in Alzheimer's.

Brodsky, who specializes in the causes and effects of misfolded proteins, believes studies of networks within cells will have broad implications for many degenerative diseases, including Alzheimer’s and Parkinson’s.  “We’re still debating what a-beta really does,” Brodsky said. “We should take a step back, and look at what the systems are.  [We should ask,] what’s the network within a cell that’s healthy, versus an amyloid-producing cell, so that you can actually read out, ‘here’s a disaster, and here isn’t.’”

Thathiah said she is encouraged by the development of tau imaging in the last few years.  “This has told us that tau develops in subcortical regions, and amyloid develops mainly in cortical regions," she said.  "When you image tau in the presence of amyloid, you have spread to cortical regions.”  She suspects some kind of “cross-Amantha Thathiah, PhDtalk” that allows a-beta to trigger the propagation of tau.

Neuroinflammation is believed to play a large role in the disease, but so far little is understood about what it does and when. “There’s a big debate,” Mathis said, “At what stage is it good or bad to have neuroinflammatory responses to those (a-beta and tau) proteins building up.” Scientists are looking at peripheral markers in cerebrospinal fluid and blood plasma, he said, “trying to get a handle on the protein damage that’s done in the brain. A-beta and tau remain the central focus, because that’s what the neuropathology shows are the hallmarks of the disease.”