Rudolph E. Tanzi, Ph.D.


Investigator
Neurology, Mass General Research Institute
Joseph P. and Rose F. Kennedy Professor of Child Neurology and Mental Retardation
Harvard Medical School
Vice-Chair
Neurology, Massachusetts General Hospital
PhD Harvard University 1990
B.S. Microbiology; B.A. History University of Rochester 1980
3d cell cultures; adam proteins; alzheimer's disease; alzheimer's in a dish; amyloid beta-peptides; amyloid beta-protein precursor; amyloid precursor protein secretases; antimicrobial cationic peptides; apolipoproteins e; ataxin-1; caspases; dementia; epigenetics; familial alzheimer's disease; gamma secretase modulators; genetic predisposition to disease; genetics of alzheimer's disease; isoflurane; metal chaperones; microglia; neurogenesis; neuroinflammation; neuroplasticity; organoid platforms; presenilin-1; presenilin/gamma-secretase

Dr. Rudolph Tanzi is the: Vice-Chair of Neurology and Director of the Genetics and Aging Research Unit, Co-Director of the McCance Center for Brain Health, and Co-Director of the MassGeneral Institute for Neurodegeneration at Massachusetts General Hospital. He also serves as the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard Medical School. 

Dr. Tanzi received his B.S. (microbiology) and B.A. (history) at the University of Rochester in 1980 and his Ph.D. (neurobiology) at Harvard Medical School in 1990. In his research achievements, Dr. Tanzi served on the team that was the first to find a disease gene with Dr. Jim Gusella (Huntington’s disease) using human genetic markers, helping to launch the field of neurogenetics. He later co-discovered all three early-onset familial Alzheimer’s disease (AD) genes, the amyloid precursor protein (APP) and the presenilin genes (PSEN1, PSEN2), with Dr. Wilma Wasco. These three gene harbor over 300 fully-penetrant mutations causing early-onset familial AD (EO-FAD). Dr. Tanzi also particpated in the first studies showing that the EO-FAD mutations increase the Abeta42:Abeta40 ratio, which increases “seeding” of plaque. With Dr. Steve Wagner, UCSD), Dr. Tanzi discovered “gamma secretase modulators” (GSM), which reverse the Abeta42:Abeta40 ratio. The GSMs are now being prepared for AD clinical trials in early-onset familial AD. With Dr. Ashley Bush, Dr. Tanzi also first showed that aggregation of beta-amyloid and alpha-synuclein is metal-dependent, which has led to ongoing clinical trials of metal chaperones in AD and Parkinson disease. With Dr. Dora Kovacs, Dr. Tanzi has also developed inhibitors of cholesteryl esters to inhibit Abeta production, and now being developed as novel AD drugs, known as ACAT inhibitors.

Dr. Tanzi has identified several other AD genes in his capacity as leader of the Cure Alzheimer’s Fund Alzheimer’s Genome Project. These genes included CD33, which he showed with Dr. Ana Gricuc to be the first microglial neuroinflammatory gene associated with AD, ADAM10, and ATXN1. His team found the first fully penetrant late-osnet AD mutations in the alpha-secretase gene (ADAM10), and, with Dr. Jaehong Suh, showed that ATXN1, the spinocerebellar gene, regulate the beta-secretase (BACE1) gene. Dr. Tanzi also co-discovered the Wilson’s disease gene and contributed to the discovery of several other neurological disease genes, inclduing the familial amyotrophic lateral sclerosis gene, SOD1, with Dr. Bob Brown. 

With Dr. Doo Yeon Kim, Dr. Tanzi used Alzheimer’s genes and human stem cells to create what the New York Times coined, “Alzheimer’s-in-a-Dish”. This is a three-dimensional human stem cell-derived neural culture system that is considered to be the first true model of Alzheimer’s disease, recapitulating both pathological hallmarks of Alzheimer’s disease: plaques and tangles. This system showed for the first time that beta-amyloid directly induce tangles, further validating the amyloid hypothesis. Using this system to screen for drugs that could be repurposed for AD, a brain permeable form of cromolyn is now in the only phase 3 AD clinical trial to target neuroinflammation.The model has made drug screening for Alzheimer’s disease 10 times cheaper and 10 times faster. Dr. Tanzi is also very active in the areas of integrative medicine and applications to brain health. Recently, Dr. Tanzi with Dr. Rob Moir demonstrated Abeta to be an antimicrobial peptide, and showed Abeta is rapidly nucleated into amyloid plaques (24 hours) when “seeded” by subclinical levels of bacteria, viruses, e.g. herpes, and other microbes entering into or activated within the brain. They are now attempting to determine which microbes trigger early beta-amyloid deposition in the brain, initiating the AD pathogenic cascade. With Dr. Se Hoon Choi, Dr. Tanzi assessed the role of hippocampal neurogenesis in AD and pharmacologically mimicked the mechanism by which exercise induces neurogenesis and BDNF to ameliorate cognition and reduce pathology in AD mice. 

Dr. Tanzi has co-authored nealry  600 research papers and has received the highest awards in his field, including the Metropolitan Life Foundation Award, Potamkin Prize, Ronald Reagan Award, Silver Innovator Award, Brain Research Foundation Award, and many others. He was named to TIME magazine’s 2015 list of TIME100 Most Influential People in the World, and received the Smithsonian American Ingenuity Award, the top national award for invention and innovation. He co-authored the popular trade books “Decoding Darkness”, the New York Times best seller, “Super Brain”, and best sellers  “Super Genes” and "The Healing Self" with Dr. Deepak Chopra. He was named by GQ magazine as a Rock Star of Science, and in his spare time, has played keyboards with the  Joe Perry and the band Aerosmith. With singer, Chris Mann, he also composed the beautiful ballad, “Remember Me”, which honors Alzheimer’s patients, and is being used to raise funds for Alzheimer’s research at the Cure Alzheimer’s Fund, for which, Dr. Tanzi serves as Chair of the Cure Alzheimer’s Fund Research Consortium.

MIND Profile Publications
tanzi@helix.mgh.harvard.edu
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