Rudy Tanzi, Ph.D.

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.

2005 to 2014
$10,641,400
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.

2012 to 2014
$3,000,000
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.

2010 to 2014
$1,600,000
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.

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.

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.

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.

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.

2006 to 2007
$200,000

Selected Publications

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

Karthikeyan Veeraraghavalu, Can Zhang, Xiaoqiong Zhang, Rudolph E. Tanzi, and Sangram S. Sisodia, Age-Dependent, Non-Cell-Autonomous Deposition of Amyloid from Synthesis of β-Amyloid by Cells Other Than Excitatory Neurons, J Neurosci, 34(10), 5 March 2014, 3668-3673
Xu Z, Dong Y, Wang H, Culley DJ, Marcantonio ER, Crosby G, Tanzi RE, Zhang Y, Xie Z, Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice, Sci Rep, 4, January 20, 2014, 3766
Jaehong Suh, Se Hoon Choi, Donna M. Romano, Moira A. Gannon, Andrea N. Lesinski, Doo Yeon Kim, Rudolph E. Tanzi, ADAM10 Missense Mutations Potentiate β-Amyloid Accumulation by Impairing Prodomain Chaperone Function, Neuron, 80(2), Oct 16, 2013, 385–401
Li A, Ahsen OO, Liu JJ, Du C, McKee ML, Yang Y, Wasco W, Newton-Cheh CH, O'Donnell CJ, Fujimoto JG, Zhou C, Tanzi RE, Silencing of the Drosophila ortholog of SOX5 in heart leads to cardiac dysfunction as detected by optical coherence tomography, Hum Mol Genet, 22(18), September 15, 2013, 3798-3806
Rudolph E Tanzi, Decoding Alzheimer's in the age of genome-wide analyses, Mol Neurodegener, 8(suppl 1), September 13. 2013, 01
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
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
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
A. Li, C. Zhou, J. Moore, P. Zhang, T.-H. Tsai, H.-C. Lee, D.M. Romano, M.L. McKee, D.A. Schoenfeld, M.J. Serra,3 K. Raygor, H.F. Cantiello, J.G. Fujimoto, and R.E. Tanzi, Changes in the Expression of the Alzheimer’s Disease- Associated Presenilin Gene in Drosophila Heart Leads to Cardiac Dysfunction, NIHPA Author Manuscripts , 8/3, May 1, 2011, 313-322
Viswanathan J, Haapasalo A, Bottcher C, Miettinen R, Kurkinen KMA, Lu A, Thomas A, Maynard CJ, Romano D, Hyman BT, Berezovska O, Nertram L, Soininen H, Dantuma NP, Tanzi RE, Hiltunen M, Alzheimer's Disease-Associated Ubiquilin-1 Regulates Presenilin-1 Accumulation and Aggresome Formation, Traffic, 12(3), Mar 12, 2011, 330-48
Brit-Maren M. Schjeide, BS; Cathrin Schnack, PhD; Jean-Charles Lambert, PhD; Christina M. Lill, MD; Julia Kirchheiner, MD, PhD; Hayrettin Tumani, MD; Markus Otto, MD; Rudolph E. Tanzi, PhD; Hans Lehrach, PhD; Philippe Amouyel, PhD; Christine A. F. von Arnim, MD; Lars Bertram, MD, The Role of Clusterin, Complement Receptor 1, and Phosphatidylinositol Binding Clathrin Assembly Protein in Alzheimer Disease Risk and Cerebrospinal Fluid Biomarker Levels, Arch Gen Psychiatry, 68(2), February 7, 2011, 207-213
Mannix RC, Zhang J, Park J, Zhang X, Bilal K, Walker K, Tanzi RE, Tesco G, Whalen MJ, Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in mice, Journal of Cerebral Blood Flow & Metabolism, 31, January 2011, 351–61
Bertram L, Lill CM, Tanzi RE, The Genetics of Alzheimer Disease: Back to the Future, Neuron, 68(2), Oct 21, 2010, 270-81
Zhang C, Browne A, Child D, Tanzi RE, Curcumin Decreases Amyloid-β Peptide Levels by Attenuating the Maturation of Amyloid-β Precursor Protein, The Journal of Biological Chemistry, 285(37), Sep 10, 2010, 28472-80
Moncaster JA, Pineda R, Moir RD, Lu S, Burton MA, Ghosh JG, Ericsson M, Soscia SJ, Mocofanescu A, Folkerth RD, Robb RM, Kuszak JR, Clark JI, Tanzi RE, Hunter DG, Goldstein LE, Alzheimer's Disease Amyloid-β Links Lens and Brain Pathology in Down Syndrome, PLoS ONE, 5(5), May 20, 2010
Zhang C, Browne A, Child D, DiVito JR, Stevenson JA, Tanzi RE, Loss-of-Function of ATXN1 Increases Amyloid-Beta Levels by Potentiating Beta-Secretase Processing of APP, Journal of Biological Chemistry, 285(12), Mar 19, 2010, 8515-26
Gianni D, Li A, Tesco G, McKay KM, Moore J, Raygor K, Rota M, Gwathmey JK, Dec GW, Aretz T, Leri A, Semigran MJ, Anversa P, Macgillivray TE, Tanzi RE, delMonte F., Protein Aggregates and Novel Presenilin Gene Variants in Idiopathic Dilated Cardiomyopathy, Circulation: Journal of the American Heart Association, 121(10), Mar 16, 2010, 1216-26
Giedraitis V, Glaser A, Sarajarvi T, Brundin R, Gunnarsson MD, Schjeide B-M, Tanzi RE, Helisalmi S, Pirttila T, Kilander L, Lannfelt L, Soininen H, Bertram L, Ingelsson M, Hiltunen M, CALHM1 P86L polymorphism does not alter amyloid-β or tau in cerebrospinal fluid, Neuroscience Letters, Volume 469, Issue 2, Jan 22 2010, 265-267
Won S, Bertram L, Becker D, Tanzi RE, Lange C., Maximizing the Power of Genome-Wide Association Studies: A Novel Class of Powerful Family - Based Association Tests, Statistics in Biosciences, 1(2), Nov 2009, 125-143
Bertram, L, Tanzi RE, Genome-wide association studies in Alzheimer's disease, Human Molecular Genetics, Vol 18, Review Issue 2, Oct 15, 2009
Kim M, Suh J, Romano D, Truong MH, Mullin K, Hooli B, Norton D, Tesco G, Elliot K, Wagner SL, Moir RD, Becker KD, Tanzi RE., Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate alpha-secretase activity., Human Molecular Genetics, Vol 18, Oct 15, 2009
Hooli BV, Tanzi RE, A current view of Alzheimer's disease, F1000 Biology Rep., 1, July 8, 2009, 54
Dong Y, Zhang G, Zhang B, Moir RD, Xia W, Marcantonio ER, Culley DJ, Crosby G, Tanzi RE, Xie Z, The Common Inhalational Anesthetic Sevoflurane Induces Apoptosis and Increases β-Amyloid Protein Levels, Archives of Neurology, Vol. 66 No. 5, May 2009
Schjeide BM, McQueen MB, Mullin K, DiVito J, Hogan MF, Parkinson M, Hooli B, Lange C, Blacker D, Tanzi RE, and Bertram L., Assessment of Alzheimer's disease case-control associations using family-based methods, Neurogenetics, DOI 10.1007/s10048-008-1051-3,, Feb 10, 2009, 568-580
Schjeide BM, Hooli B, Parkinson M, Hogan MF, DiVito J, Mullin K, Blacker D, Tanzi RE, Bertram L, GAB2 as an Alzheimer Disease Susceptibility Gene, Follow up of Genomewide Association Results, Arch Neurol, 66, Feb 2009, 250 – 254
Bertram L, Schjeide BM, Hooli B, Mullin K, Hiltunen M, Soininen H, Ingelsson M, Lannfelt L, Blacker D, Tanzi RE., No association between CALHM1 and Alzheimer's disease risk., Cell, 135(6), Dec 12 2008, 993-4
Xie Z, Culley DJ, Dong Y, Zhang G, Zhang B, Moir RD, Frosch MP, Crosby G, Tanzi RE. , The common inhalation anesthetic isoflurane induces caspase activation and increases Aβ level in vivo., Annals of Neurology, Volume 64, Dec 2008
Cotton RG, Auerbach AD, Axton M, Barash CI, Berkovic SF, Brookes AJ, Burn J, Cutting G, den Dunnen JT, Flicek P, Freimer N, Greenblatt MS, Howard HJ, Katz M, Macrae FA, Maglott D, Möslein G, Povey S, Ramesar RS, Richards CS, Seminara D, Smith TD, Sobrido MJ, Solbakk JH, Tanzi RE, Tavtigian SV, Taylor GR, Utsunomiya J, Watson M, The Human Variome Project, Science., 322(5903), Nov 7 2008, 861-2
Bertram L, Lange CL, Mullin K, Parkinson M, Hsiao M, Hogan MF,  Schjeide BMM, Hooli B, DeVito J, Ionita I, Jiang H, Laird N, Moscarillo T, Ohlsen KL, Elliott K, Wang X, Hu-Lince D, Ryder M, Murphy A, Wagner SL, Blacker D, Becker KD, Tanzi RE., Genome-wide Association Analysis Reveals Putative Alzheimer's Disease Susceptibility Loci in Addition to APOE, Am. J. Hum. Genet., 83, November 2008, 623-632
Bertram L, Tanzi RE, Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses, Nature Reviews Neurosci., October 2008
Schaffer B, Bertram L, Miller L, Mullin K, Weintraub S, Johnson N, Bigio E, Mesulam M, Wiedau-Pazos M, Jackson G, Cummings J, Cantor R, Levey A, Tanzi RE, and Geschwind D, Association of GSK3B with Alzheimer's Disease and Frontotemporal Dementia, Arch. Neurol., 65(10), October 2008, 1368-1374
Zhang B, Dong Y, Zhang G, Moir RD, Xia W, Yue Y, Tian M, Culley DJ, Crosby G, Tanzi RE, Xie Z, The inhalation anesthetic desflurane induces caspase activation and increases amyloid-beta protein levels under hypoxic conditions., J Biol Chem., 2;283(18), May 2, 2008, 11866-75
Zhang G, Dong Y, Zhang B, Ichinose F, Wu X, Culley DJ, Crosby G, Tanzi RE, Xie Z., Isoflurane-induced caspase-3 activation is dependent on cytosolic calcium and can be attenuated by memantine., J Neurosci, 28, April 23, 2008, 4551-60
Tesco G, Koh YH, Kang E, Cameron A, Das S, Sena-Esteves M, Hiltunen, Yang S-H, Zhong Z, Shen Y, Simpkins J, Tanzi RE., Depletion of GGA3 stabilizes BACE and enhances β-secretase activity, Neuron, 54(5), 2007, 721-37
Kim M, Hersh LB, Leissring MA, Ingelsson M, Matsui T, Farris W, Lu A, Hyman BT, Selkoe DJ, Bertram L, Tanzi RE, Decreased catalytic activity of the insulin degrading enzyme in chromosome 10-linked Alzheimer’s disease families., Journal of Biological Chemistry, 282(11), 2007, 7825-32
Xie Z, Dong Y, Maeda U, Moir R, Xia W, Culley DJ, Crosby G, Tanzi RE., The Inhalation Anaesthetic Isoflurane Induces a Vicious Cycle of Apoptosis and Aβ Accumulation., J. Neurosci., 27, 2007, 1247-1254
McQueen MB, Bertram L, Lange C, Becker KD, Albert MS, Tanzi RE, Blacker D., Exploring Candidate Gene Associations with Neuropsychological Performance., Am J Med Genet B Neuropsychiatr Genet, 144(8), 2007, 987-91