Today we have Dr. Karl Herrup, a neurobiologist known for his investigations into the roles that DNA damage and noncoding genetic variants have in Alzheimer’s disease. Joining Ken today to interview Karl is Dr. Tommy Wood, a visiting scientist here at IHMC.  Tommy also is an associate professor of pediatrics and neuroscience at the University of Washington, where he focuses on brain health across lifespan. He has been our guest several times on STEM-Talk and we will have links to those interviews in our show notes for today’s episode. After more than a century of research, the underlying cause of Alzheimer’s remains a mystery. For the past few decades, the leading theory has been the amyloid cascade hypothesis, which proposes that abnormal amyloid plaques in the brain are the central cause of the disease. Today we talk to Karl about his lab and research as well as his view that the amyloid cascade hypothesis is not only flawed,  but also could be holding back research for a cure of Alzheimer’s. A professor of neurobiology and an investigator in the Alzheimer’s Disease Research Center at the University of Pittsburgh School of Medicine, Herrup is the author of How Not to Study a Disease: The Story of Alzheimer’s. Show notes: [00:03:50] Tommy asks Karl what he was like as a kid to open the interview. [00:04:36] Tommy asks Karl about his educational environment growing up. [00:05:10] Ken mentions that Karl went to Brandies University originally with the intent of becoming a physician and asks Karl what happened to change his mind. [00:06:14] Ken asks Karl if it is true that his father was disappointed with Karl’s decision to abandon medical school in favor of genetics. [00:07:02] Tommy mentions that Karl began researching genetics in the late 1960s when researchers were just beginning to unravel the secrets of DNA. Tommy asks Karl to discuss why this was such an exciting time to study genetics. [00:08:38] Tommy asks Karl what prompted him to pursue a PhD in neuroscience. [00:11:34] Continuing on the theme of happy accidents, Ken asks if it was also an accident that led to Karl moving to Switzerland for a second post-doc. [00:12:36] Ken asks Karl to expound on his experience taking an overseas post-doc, which was not a common practice in the 1970s. [00:14:11] Ken mentions that Karl has seemed to benefit in his life from the combination of preparation and the willingness to explore opportunities that present themselves. [00:15:00] Tommy mentions that when Karl arrived back in the US from Switzerland, he accepted a faculty position at Yale and asks him to discuss this experience. [00:17:06] Tommy mentions that after Yale, Karl had several faculty appointments, including a seven-year stint in Hong Kong, and asks Karl to talk about that experience. [00:21:36] Tommy asks Karl why, in 2019, he moved back to his hometown to become a professor of neurobiology at the University of Pittsburgh and co-investigator at the university’s Alzheimer’s research center. [00:24:45] Ken asks Karl to talk about his lab at the University of Pittsburgh, which focuses on the biology of neurodegeneration. [00:26:32] Ken asks Karl if there was anything specific that caused him to shift his focus at this stage in his career so heavily towards Alzheimer’s research. [00:28:21] Tommy comments on Karl’s hypothesis of the aging brain, noting that it would make sense for the same processes involved in the developing brain to relate to what we see in the aging brain, as these processes are continuous throughout the lifespan. [00:29:54] Tommy pivots to talk about Karl’s book, entitled “How Not to Study a Disease: The Story of Alzheimer’s” for which Karl interviewed a number of experts and colleagues, asking each one to define Alzheimer’s disease in their own words. [00:30:51] Tommy reiterates the point that we still do not have a universally accepted definition of Alzheimer’s disease and asks Karl wh...