Rudy Tanzi, Ph.D.

Headshot photo

Dr. Rudolph Tanzi serves as Chair of the Cure Alzheimer’s Fund Research Consortium. He is also the Joseph P. and Rose F. Kennedy Professor of Neurology at Harvard University and Director of the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH). 

Dr. Tanzi has been a pioneer in genetic studies of neurological disease since the 1980’s when he participated in the first study that to use genetic markers to find a disease gene (Huntington's disease). Dr. Tanzi co-discovered the three familial early-onset Alzheimer's disease (AD) genes and several other neurological disease genes including that responsible for Wilson’s disease. As leader of the Cure Alzheimer’s Fund Alzheimer’s Genome Project, Dr. Tanzi has carried out multiple genome wide association studies of thousands of Alzheimer’s families leading to the identification of over 100 novel AD candidate genes, including CD33. His research on the role of zinc and copper in AD has led to clinical trials of the drug PBT2. Dr. Tanzi serves on dozens of editorial and scientific advisory boards, and has received the two highest awards for Alzheimer's disease research: The Metropolitan Life Award and The Potamkin Prize. He has published over 425 research articles and  co-authored the popular trade books “Decoding Darkness” and the recent New York Times Bestseller, “Super Brain”.  

 

Funded Research

Project Description Researchers Funding
Alzheimer’s Genome Project™

The goal of this project is to evaluate our new Alzheimer’s disease gene candidates for effects on Alzheimer’s pathology and related biological pathways, including APP processing, amyloid beta protein generation, tangle formation and cell death. These studies are being carried out as part of Phase II of the Alzheimer’s Genome Project (AGP) and entail functional analyses of the Alzheimer’s gene candidates identified in Phase I of the AGP.

 Rudy Tanzi, Ph.D. 2005 - 2013
$7,641,000
The Amylin Protein of Diabetes Mellitus is an Antimicrobial Peptide

The goal of this project is to determine whether the amylin (IAPP) protein has a role in innate immunity (similar to Abeta) in order to significantly advance our understanding of the origins of diabetes pathology and its possible linkage to Alzheimer’s disease.
Robert Moir, Ph.D.
Rudy Tanzi, Ph.D.
 2010 - 2013
$900,000
Whole Genome Sequencing

We will carry out Whole Genome Sequencing (WGS) of all subjects in the National Institute of Mental Health (NIMH) Alzheimer’s disease family sample (1,510 subjects; 437 AD families). We will identify functional DNA variants throughout the human genome that are inherited as risk factors for Alzheimer’s disease. We also will analyze DNA from brain samples of subjects who exhibited significant Alzheimer’s pathology at autopsy, but never suffered from dementia; this will allow us to identify protective gene variants as well.

 Rudy Tanzi, Ph.D. 2012
$750,000
Curcumin Collaborative Project

This collaborative project will identify and characterize novel curcumin-like derivatives for the treatment and prevention of Alzheimer’s disease. The purpose of the study is to develop means of overcoming obstacles to rapid breakdown and creating methodologies for precisely delivering curcumin derivatives to appropriate locations within the brain.
William Klunk, MD, Ph.D.
Rudy Tanzi, Ph.D.
 2010
$400,000
Novel Soluable Gamma-Secretase Modulators

Building on in vitro characterization of a novel series of soluable gamma-secretase modulators (SGSMs) funded by Cure Alzheimer’s Fund, the current project is a thorough pharmacological or in vivo examination of these molecules to identify the best or “lead” drug candidate.
Steve Wagner, Ph.D.
Rudy Tanzi, Ph.D.
 2010
$250,000
Potential for Host Cytotoxicity from Microbially-derived Abeta Oligomers

Alzheimer’s disease (AD) is the most common form of dementia in the elderly afflicting over 20 million people worldwide. Two decades of findings from cell biology, genetic, neuropathological, biochemical and animal studies overwhelmingly point to the β-amyloid peptide (Aβ) as the key protein in the disease’s pathology (see review by Hardy and Selkoe, 20001). Aβ appears to be a soluble component of normal brain. However, in AD brain the peptide accumulates as β-amyloid, an insoluble semi-crystalline deposit that is the hallmark of the disease pathology.
Rudy Tanzi, Ph.D.
Robert Moir, Ph.D.
Charles Glabe, Ph.D.
 2009
$250,000
Investigation of Certain Properties of Mitochondria Membranes Related to AD

While the mechanism of Aβ cytotoxicity remains contentious, evidence is accumulating that membrane permiabilization plays a key role in the pathological activity of the peptide. This study will focus on role of Aβ oligomerization in the Aβ-mediated disruption of lipid bilayers.
Robert Moir, Ph.D.
Rudy Tanzi, Ph.D.
 2008
$200,000
Identification of Agents that Inhibit the Generation and Neurotoxicity of Cross-linked B-amyloid Protein Species

We have coined the term CAPS to describe cross-linked-Beta-amyloid protein species. CAPS, particularly dimeric forms, are highly neurotoxic. CAPS are also abundant in vivo, with dimeric species alone comprising as much as 40 percent of the total Abeta pool in late state AD brain. In this study we plan to screen compound libraries for potential therapeutic agents that attenuate the levels and/or cytotoxic activity of CAPS.
Robert Moir, Ph.D.
Rudy Tanzi, Ph.D.
 2006 - 2007
$200,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Zhongcong Xie, MD, PhD,∗ Sayre McAuliffe,∗ Celeste A. Swain,∗ Sarah A. P. Ward,∗ Catherine A. Crosby,∗ Hui Zheng,† Janet Sherman,‡ Yuanlin Dong,∗ Yiying Zhang,∗ Neelakantan Sunder,§ Dennis Burke,¶ Kevin Washicosky,|| Rudolph E. Tanzi,|| and Edward R. Marcantonio∗∗ , "Cerebrospinal Fluid Aβ to Tau Ratio and Postoperative Cognitive Change" , Annals of Surgery , Ann Surg 2013;00 , 5/10/2013 , 1-6
BV Hooli1, ZM Kovacs-Vajna2, K Mullin1, MA Blumenthal1, M Mattheisen3, C Zhang1, C Lange4, G Mohapatra5, L Bertram6 and RE Tanzi1 , "Rare autosomal copy number variations in early-onset familial Alzheimer’s disease" , Molecular Psychology , 6/11/2013
Wagner SL, Tanzi RE, Mobley WC, Galasko D , "Potential Use of γ-Secretase Modulators in the Treatment of Alzheimer Disease" , Arch Neurol. , July 16, 2012
Wu X, Lu Y, Dong Y, Zhang G, Zhang Y, Xu Z, Culley DJ, Crosby G, Marcantonio ER, Tanzi RE, Xie Z , "The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-α, IL-6, and IL-1β" , Neurobiology of Aging , 33(7) , July 2012 , 1364-78
B.V. Hooli, PhD, G. Mohapatra, PhD, M. Mattheisen, MD, A.R. Parrado, PhD, J.T. Roehr, MS, Y. Shen, PhD, J.F. Gusella, PhD, R. Moir, PhD, A.J. Saunders, PhD, C. Lange, PhD, R.E. Tanzi, PhD and L. Bertram, MD , "Role of common and rare APP DNA sequence variants in Alzheimer disease" , Neurology 78 , 78/16 , April 17, 2012 , 1250-1257
Xie Z, Dong Y, Maeda U, Xia W, Tanzi RE , "RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing" , Transl Neurodegener. , 1:8 , Mar 22, 2012
Lill CM, Roehr JT, McQueen MB, Kavvoura FK, Bagade S, Schjeide BM, Schjeide LM, Meissner E, Zauft U, Allen NC, Liu T, Schilling M, Anderson KJ, Beecham G, Berg D, Biernacka JM, Brice A, DeStefano AL, Do CB, Eriksson N, Factor SA, Farrer MJ, Foroud T, Gasser T, Hamza T, Hardy JA, Heutink P, Hill-Burns EM, Klein C, Latourelle JC, Maraganore DM, Martin ER, Martinez M, Myers RH, Nalls MA, Pankratz N, Payami H, Satake W, Scott WK, Sharma M, Singleton AB, Stefansson K, Toda T, Tung JY, Vance J, Wood NW, Zabetian CP; 23andMe Genetic Epidemiology of Parkinson's Disease Consortium; International Parkinson's Disease Genomics Consortium; Parkinson's Disease GWAS Consortium; Wellcome Trust Case Control Consortium 2), Young P, Tanzi RE, Khoury MJ, Zipp F, Lehrach H, Ioannidis JP, Bertram L , "Comprehensive research synopsis and systematic meta-analyses in Parkinson’s disease genetics: The PDGene database" , PLoS Genet. , 8(3) , March 2012 , e1002548
Yiying Zhang MD, MS1, Zhipeng Xu MD, PhD1, Hui Wang MD1,2, Yuanlin Dong MD, MS1, Hai Ning Shi PhD, DVM3, Deborah J. Culley MD4, Gregory Crosby MD4, Edward R. Marcantonio MD5, Rudolph E. Tanzi PhD.6, Zhongcong Xie MD, PhD1,* , "Anesthetics Isoflurane and Desflurane Differently Affect Mitochondrial Function, Learning, and Memory" , Annals of Neurology , Volume 71, Issue 5 , February 24, 2012 , 687–698
Sungho Wona, Qing Luc, Lars Bertram, Rudolph E. Tanzi, Christoph Lange , "On the Meta-Analysis of Genome-Wide Association Studies: A Robust and Efficient Approach to Combine Population and Family-Based Studies" , Human Heredity , 73 , January 18, 2012 , 35-46
Sarajärvi T, Tuusa JT, Haapasalo A, Lackman JJ, Sormunen R, Helisalmi S, Roehr JT, Parrado AR, Mäkinen P, Bertram L, Soininen H, Tanzi RE, Petäjä-Repo UE, Hiltunen M , "Cysteine 27 Variant of the δ-Opioid Receptor Affects Amyloid Precursor Protein Processing through Altered Endocytic Trafficking" , Mol Cell Biol. , 31(11) , June 2011 , 2326–2340
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