Virginia Lee & John Trojanowski on the Protein Road Map to Alzheimer's
Special Topic of Alzheimer's Disease Interview, December 2011
What We Now Know About Alzheimer's…
Lee believes this biomarker, and others like it, is a very important piece of knowledge in the fight against Alzheimer's. "With Alzheimer's, you have a whole head full of plaque, tangle, Lewy body, and TDP-43 pathology that needs treatment options," she explains, "and those options have to address both the plaques and the tangles in all Alzheimer patients, as well as Lewy body and TDP-43 pathology in a large subset of Alzheimer patients. So in terms of real drugs based on disease-modifying knowledge obtained over the past 25 years, I would say it's still a work in progress, because the clinical trials are still ongoing, and most of these trials are still centered, one way or another, around reducing beta-amyloid plaques.
"Whether drugs that only target beta-amyloid will work isn't clear, but the thinking is that if you can identify patients at the early stages of Alzheimer's disease who have these beta-amyloid plaques—and this is something that John and the people at ADNI are working on now—then it might be possible to prevent further beta-amyloid deposition and abrogate the disease process.
Trojanowski emphasizes the amazing progress that has been made in the past 25 years. "Prior to the 1990s, I'd be working with a support group, and someone would say to me, 'Doc, you know my wife has Alzheimer's. When will there be a drug?' It almost brought tears to my eyes as a physician to have to say, 'I don't know. I have no idea.' Because back then, all we knew was A-beta and a gene called APP that encoded the protein. We didn't know tau formed tangles, we didn't know about mutations in the genes, we didn't know alpha-synuclein formed Lewy bodies—I would say the amazing progress in the 1990s was the equivalent of making the blind see.
"So we can now see all these things, and that is huge. We have the people, we have the ideas, we have the hypotheses. I now tell people in support groups who ask me that question, 'We are within striking distance of finding disease-modifying therapies for Alzheimer's disease.' And I don't mean to be provocative—it's true. But, we lack the resources to test all the preclinical compounds to advance them to clinical trials. It's a matter of money. The American public needs to realize that the solution to Alzheimer's is in their hands because more resources for research on Alzheimer's and related disorders will accelerate the pace of progress.
"I would say the amazing progress in the 1990s was the equivalent of making the blind see."
–John Trojanowski
"By this, I mean that, for example, that if we could delay the onset of the Alzheimer's disease for five years, if we had a drug today to do that, delay the onset for five years, by 2050 the incidence and prevalence of Alzheimer's would be nearly half what it would otherwise be—and so would the $3 trillion price tag of caring for those affected.
"If you change the onset of Alzheimer's from age 75 to 80, that would mean many fewer people would develop Alzheimer's disease in their lifetime and this would have a huge impact on our economy as well as the epidemic of people who would otherwise succumb to Alzheimer's disease. Thus, if you run the numbers and look at the demographics, a delay of five years is huge both economically and personally.
"Of course we would love it if we could find a preventative, some sort of drug that we could give to someone in their 40's, the way people take blood-pressure-lowering drugs today and cut their risk for stroke or heart attack down to the level of those who don't have hypertension. Those are the kinds of things we dream about in our wildest dreams—the Holy Grail. But delaying Alzheimer's disease onset by five years is not a bad thing at all."
When asked if the five-year delay is a more realistic idea than the preventative "Holy Grail" dreams, Trojanowski is affirmative, but Lee is more skeptical. "Maybe, maybe not," she says. "I'm not as confident as John is that this is possible."
"If we had the money that was spent on the war in Iraq, I guarantee you we would, Virginia!" John exclaims. "This is a priority that we as Americans have to embrace. We are the wealthiest country in the world, and we make choices how to spend our money. We spend our money on wars; we spend $6 billion a year on Viagra and Cialis, $2 billion a year on popcorn, which is more than we as a nation spend on Alzheimer's. Over $50 billion is spent by Americans every year on anti-aging creams, potions and lotions that do absolutely nothing, so there are resources flowing through our economy and we need to make wiser choices on how we invest those resources, and I think that investing in finding a cure for Alzheimer's should be a national as well as global imperative because the Alzheimer epidemic is global.
"We are making choices as citizens about spending our resources and we have to ask ourselves the question, is how we use our precious resources now ethical? Is it right not to apply more resources to the fight against such increasingly common killers such Alzheimer's, Parkinson's, frontotemporal degeneration, and Lou Gehrig's diseases? Is that what we should be doing as a society when we are in the throes of an epidemic of Alzheimer's that I think will make the horrible natural disasters in Japan pale by comparison? Due to dwindling resources and the growing number of patients, the prospect is real that we will have increasing numbers of homeless Alzheimer's patients walking the streets of America in the next 20 years."
"…John and I recognized, back in the beginning of our work together, that to understand these diseases you really have to start with the human brain."
–Virginia Lee
Trojanowski related much of this perspective in a documentary he participated in for PBS called Alzheimer's Disease: Facing the Facts, which also featured Lee and other Alzheimer's researchers, such as Ron Petersen from the Mayo Clinic in Rochester, John Morris from Washington University in St. Louis, and Carl Cotman from the University of California, Irvine, as well as Alzheimer's patients and their families.
Trojanowski jokes that Lee will say that everything he's said is wrong, but although she kids back that he loves to get on his soapbox to anyone who will listen to his urgent pleas for an national Alzheimer program like the "Man on the Moon" or Panama Canal projects, she also agrees with him, particularly in the current climate of tightening government funding for research.
Another issue looming is the loss of American leadership in creating new intellectual property related to curing disease like Alzheimer's disease that helps with job creation focused on developing better therapies and diagnostics. Looking at the Special Topics analysis, the overwhelming majority of the research and citations are US-based, but Lee and Trojanowski fear that this may not be the case for much longer.