Episode 174: Rudy Tanzi talks about genetics, aging and the hallmarks of Alzheimer’s
STEM-Talk
Unraveling Alzheimer's: Genetics and Breakthroughs
This chapter explores the evolving understanding of Alzheimer's disease, emphasizing genetic factors, amyloid plaques, and neuroinflammation. It highlights significant research advancements and the pivotal roles of genes CD33 and TREM2 in the disease's development and potential treatment.
Today we have Dr. Rudolph E. Tanzi, who is perhaps best known for co-discovering all three familial early-onset Alzheimer’s disease genes. In addition, Rudy’s lab was the first to use human stem cells to create three-dimensional human brain organoids and three-dimensional neural-glial culture models of Alzheimer’s disease, which became known as “Alzheimer’s-in-a-Dish.” These models were the first to recapitulate all three of the key pathological hallmarks of Alzheimer’s disease and have made drug screenings faster and cheaper.
Rudy is the director of the Genetics and Aging Research Unit as well as the director of the Henry and Allison McCance Center for Brain Health. Rudy is also co-Director of the Massachusetts General Institute for Neurodegenerative Disease at Massachusetts General Hospital and serves as the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School.
Rudy has published more than 700 research papers and is one of the top 50 most cited neuroscientists in the world. He is author of “Decoding Darkness,” and a co-author of two books with Deepak Chopra, “Super Brain” and “The Healing Self.”
Show notes:
[00:03:18] Ken opens the interview mentioning that Rudy began playing the accordion when he was just seven years old. Ken goes on to ask Rudy about the time his father gave him a Jimmy Smith album and some advice.
[00:05:51] Ken mentions that, in addition to Rudy’s musical talents, he was also interested in science growing up. Ken asks about Rudy’s participation in the Westinghouse Science Talent Search and what that experience was like.
[00:07:09] Ken asks Rudy about growing up in Cranston, Road Island.
[00:08:39] Rudy talks about how he ended up at the University of Rochester after high school.
[00:09:51] Ken mentions that both Rudy’s grandfather and father passed away at the age of 45. Ken asks Rudy if this played a role in his pursuit of a career in genetics research.
[00:10:57] Rudy explains how he chose Harvard Medical School for his Ph.D.
[00:12:47] Ken pivots to ask Rudy about his time working with Jim Gusella in the early 80’s at Mass General, where they were the first to ever find a disease gene. Family studies at the time had shown that the Huntington’s disease gene was linked to a polymorphic DNA marker. Rudy talks about this discovery and how the chromosomal localization of the Huntington’s disease gene was the first step in using recombinant DNA technology to identify the primary genetic defect in this disorder.
[00:16:07] Ken asks Rudy about his work in 1987, when he discovered the first Alzheimer’s gene, recombinant DNA technology, which causes the production of amyloid. Ken goes on to explain that mutations in the APP gene can cause a rare form of early onset Alzheimer’s. Rudy talks about the paper that came out in “Science” that detailed this discovery.
[00:18:38] Rudy discusses his personal philosophy and approach to research.
[00:19:43] Ken mentions that in Rudy’s book, Decoding Darkness, he writes that few nightmares on Earth can compare to Alzheimer’s disease. Ken asks Rudy to talk more about this book.
[00:21:50] Ken explains that in the same way our physical capabilities will suffer some form of decline with age, it is also expected that we have some decline in memory and cognitive ability as we age as well. However, Ken goes on to say that when people begin to experience age-related memory lapses, it can lead to a lot of anxiety about their genetic predisposition to Alzheimer’s. Ken asks Rudy to talk about the lifestyle factors that play into whether someone predisposed to develop Alzheimer’s can stave off or avoid disease development.
[00:26:09] Ken explains that aging appears to intensify when people stop challenging themselves with new things. Given this, Ken asks Rudy what his thoughts are on challenging our brains as they age to protect our cognitive abilities.
[00:29:08] Ken asks Rudy about the principal advances in Alzheimer’s research that have occurred over the past few decades. He also asks Rudy for his thoughts on the biggest and most important mysteries that remain regarding Alzheimer’s.
[00:34:48] Ken brings up one of Rudy’s papers, published in 2014, which they successfully recapitulated amyloid-β and tau pathology in a single 3D human neural cell culture system. Ken goes on to mention that this paper had a huge impact in the field of research, and even landed Rudy a spot on Time Magazine’s 100 most influential people list.
[00:38:57] Ken mentions that in 2019, Rudy published another influential paper, which investigated the crosstalk between microglial receptor genes CD33 and TREM2. Ken explains that these two genes have been associated with an increased risk of Alzheimer’s disease, and that Rudy has referred to them as yin and yang to each other. Ken asks Rudy to elaborated on this concept.
[00:43:00] Ken pivots to discuss Rudy’s paper that was published last year and which the press somewhat misleadingly reported on. Ken explains that physical exercise has been shown to reduce amyloid beta in various Alzheimer’s models, but it is imperfectly associated with amyloid burden in humans. Ken goes on to explain that Rudy’s paper demonstrated, for the first time, a cellular and molecular mechanism by which exercise induced irisin attenuates amyloid beta pathology.
[00:46:27] Ken mentions that Rudy is currently writing a new book and mentions that some of Rudy’s previous books have been co-authored with Deepak Chopra. Ken asks how Rudy and Deepak came to work together.
[00:51:24] Ken asks, given the complex nature of Alzheimer’s and the many components that contribute to the pathology, if there is a way to organize all we know about Alzheimer’s in a straight-forward way.
[00:58:19] Ken asks if there are any particularly promising FDA approved drugs or nutraceuticals for stopping the production of amyloid.
[01:00:16] Ken asks if Rudy gets questions regarding which drugs and supplements screened have shown the most promise.
[01:03:33] Ken closes the interview by asking how he manages to be such a prolific scientist. Rudy has published more 700 papers while also having a lifetime of playing music with rock bands, working with sports teams and publishing New York Times best sellers.
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