Rudolph E. Tanzi

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Rudolph E. Tanzi

Rudolph Emile 'Rudy' Tanzi (born September 18, 1958) a professor of Neurology at Harvard University, vice-chair of neurology, director of the Genetics and Aging Research Unit, and co-director of the Henry and Allison McCance Center for Brain Health at Massachusetts General Hospital (MGH). [1]

Contents

Tanzi has been investigating the genetics of neurological disease since the 1980s. [2] He co-discovered all three familial early-onset Alzheimer's disease (FAD) genes and several other neurological disease genes including that responsible for Wilson’s disease. [3] His team was the first to use human stem cells to create three-dimensional cell culture organoids of AD, dubbed “Alzheimer's-in-a-Dish”. [4] [5] The 3-D model made drug screening for AD faster and more cost-effective.

He has published over 600 research papers and has received the highest awards in his field, including the Potamkin Prize. Tanzi on occasion serves as a studio keyboard player for Aerosmith and other musicians. [6]

Early life and education

Tazi is a native of Cranston, Rhode Island. Tanzi received his B.S. in microbiology and B.A. in history from the University of Rochester in 1980. In 1990, he received his Ph.D. in neurobiology at Harvard Medical School, where his doctoral thesis was on the discovery and isolation of the gene that encodes amyloid precursor protein, the precursor to beta-amyloid which is a pathological hallmark of Alzheimer's disease and generally accepted as the central driver of the disease. [7] The results were published in Science, [8] more or less simultaneously with two other groups in 1986 and 1987. [7]

Career

At the start of his career in 1980, Tanzi worked as a research technologist for James Gusella at Massachusetts General Hospital. There, he assisted in localizing the Huntington's disease gene; his findings were published in Nature in 1983.

In 1987, based on his doctoral studies at Harvard Medical School, he was the lead author of seven papers published in Science and Nature between 1987 and 1988, describing the initial cloning, mapping, and characterization of the gene encoding the amyloid beta-protein precursor (APP). Two other groups reported the cloning of APP at that time, and the gene was shown in 1990 to contain a mutation causing Dutch cerebral hemorrhage with amyloidosis and later in 1991, a mutation causing early-onset familial AD (EO-FAD). In 1992, Tanzi and ex-trainee, Wilma Wasco, discovered the two APP family members, APLP1 and APLP2.

In 1995, Tanzi collaborated with Peter Hyslop and Jerry Schellenberg to discover the two other EO-FAD genes, presenilin 1 and 2 (PSEN1 and PSEN2). He has published many key studies characterizing the role of the EO-FAD genes in health and disease. All three genes remain among the most highly studied drug targets in the field of AD, especially about therapeutic strategies aimed at reducing beta-amyloid deposition. In 1993, Tanzi also first discovered the gene for the neurodegenerative disease, Wilson's disease; his findings were published in Nature Genetics . In that same year, he contributed to the discovery of the first familial amyotrophic lateral sclerosis (ALS) gene, SOD1, by providing the key genetic and physical mapping data for chromosome 21 used to find the gene defect.

As the leader of the Cure Alzheimer's Fund's Alzheimer's Genome Project, Tanzi several other AD genes, most notably, CD33, reported in 2008 with his ex-trainee, Lars Bertram, in the American Journal of Human Genetics . In that study, Tanzi reported the first family-based genome-wide association study of AD, which most notably to the identification of the first innate immune AD gene, CD33, which encodes a cell-surface receptor on monocytes and microglia. When first identified as an AD gene, nothing was known about CD33 in the brain or AD pathology. In 2013, Tanzi and his ex-trainee, Ana Griciuc first reported in Neuron that increased expression of CD33 in microglial cells in AD brain and showed that a protective CD33 gene variant was associated with reductions in CD33 expression and Abeta levels in AD brain. Importantly, they showed CD33 inhibits microglial phagocytosis and clearance of Abeta and induces pro-inflammatory cytokine release leading to neuroinflammation. They also elucidated the molecular mechanism by which sialic acid binds to CD33 to induce neuroinflammation.

In a follow-up study published in Neuron in 2019, Tanzi and Griciuc compared the neuroinflammatory effects of the CD33 gene to another AD-associated innate immune gene, TREM2. Knockout of CD33 in AD mice attenuated amyloid-beta pathology and improved cognition while knockout of TREM2 led to opposite effects. They then showed that TREM2 functions downstream of CD33 and that crosstalk between CD33 and TREM2 involves the neuroinflammation-related IL-1beta/IL-1RN axis cluster. CD33 has now emerged as the primary target for novel drug discovery programs aimed at curbing neuroinflammation, at over a dozen pharmaceutical and biotech companies.

Other AD genes Tanzi has discovered include ADAM10, UBQLN1, IDE, A2M, ITGB3, and ATXN1. In 2019, Tanzi, his ex-trainee, Jaehong Suh, and Huda Zoghbi (Baylor) led a study published in the journal, Cell , showing that ATXN1 (encoding the spinal cerebellar ataxia gene product, Ataxin-1) controls the production of the amyloid beta protein by regulating the expression of the gene BACE1.

Over the past two decades, Tanzi has also contributed to the development of novel therapeutics for AD. Beginning in 1994, in a study published in Science with his post-doctoral fellow Ashley Bush, Tanzi demonstrated a key role for zinc, copper, and iron in beta-amyloid deposition and Lewy body formation. This finding has led to the initiation of AD clinical trials of metal chaperones targeting metal-induced aggregation of beta-amyloid in AD and of alpha-synuclein and Lewy bodies in Parkinson's disease.

In 2000, Tanzi and Steven Wagner began screening for a class of drugs that they termed "gamma secretase modulators (GSM)". GSM's reverse the Abeta42:Abeta40 ratio and thereby prevent the “seeding” of amyloid plaques. Notably, they do not inhibit gamma-secretase. Tanzi and Wagner have published several papers on these compounds. Their ongoing drug development efforts supported by the National Institutes of Health Neurotherapeutics Blueprint Program and the Cure Alzheimer's Fund, have led to a clinical candidate GSM that is now slated for AD clinical trials.

Also in 2000, Tanzi collaborated with cell biologist, Dora Kovacs, to show that blocking the enzyme acetyl-coA acetyltransferase 1 (ACAT1), responsible for storing cholesterol as lipid droplets in intracellular rafts, prevents the generation of Abeta. Most recently, this led to their discovery that ACAT1 promotes the palmitoylation of APP dimers in lipid rafts, rendering them more susceptible to beta-secretase cleavage and Abeta production. They are now testing anti-palmitoylation drugs as well as their ACAT1 inhibitors as potential drugs for preventing the axonal release of Abeta and reducing beta-amyloid deposition.

In 2005, Tanzi and his ex-trainee and late colleague, Robert Moir, reported in the Journal of Biological Chemistry the existence of auto-antibodies against oligomeric Abeta, which they showed to protect against risk for AD. This discovery inspired Roger Nitsch and the Swiss biotech, Neurimmune to develop an AD therapy based on isolating those auto-antibodies from memory B-cells and reverse translating them into the promising beta-amyloid immunotherapy, known as aducanumab, which was recently successful in a phase 3 AD clinical trial by Biogen and Eisai.

In 2014, Tanzi, and his ex-trainees, Doo Yeon Kim and Se Hoon Choi, were the first to use human stem cells to create three-dimensional cell culture organoids of AD, dubbed by The New York Times as “Alzheimer's-in-a-Dish”. This model was the first to recapitulate all three key AD pathological hallmarks in vitro, and, most importantly, resolved a decades-long debate as to whether Abeta pathology causes the formation of neurofibrillary tangles. Using this system, they were the first to definitively show that amyloid plaques directly cause neurofibrillary tangles, something that could not be shown in mouse models of early-onset familial AD gene mutations in APP and the presenilins (owing to differences in mouse and human isoforms of the Tau protein, the principal component of neurofibrillary tangles). This 3-D cell culture model/human brain organoid system of AD has also made drug screening considerably faster and more cost-effective. Most recently, using a modified 3-D human stem cell-derived neural-glial cell AD model, Tanzi has helped develop therapies targeted against neuroinflammation in AD. These include ALZT-OP1 (AZTherapies) targeting microglial activation and neuroinflammation, and a neuroprotective drug combination, called AMX0035 (Amylyx, co-founded by Josh Cohen, Justin Klee with Tanzi serving as the founding chair of the Scientific Advisory Board). AMX0035 was successful in a phase 2 clinical trial of ALS and is now under consideration for approval by the FDA, while it is also being tested in a phase 2 clinical trial in AD patients.

In another set of groundbreaking studies, Tanzi, working with Robert Moir, investigated whether amyloid beta (Abeta) may play a normal role in the brain. They demonstrated Abeta to be a potent antimicrobial peptide (AMP) in the brain's innate immune system. After showing that the beta-amyloid protein protects against various infections in different animal models ranging from C. elegans to mouse models, they made an even more striking discovery. They showed that subclinical levels of microbes can rapidly seed (nucleate) amyloid plaques. It has long been held that amyloid plaques require a decade or more to form in the brain. However, injecting either bacteria or virus into the hippocampus of very young AD mice, showed that amyloid plaques formed overnight. These findings suggest that even subclinical levels of bacteria, viruses, or other microbes, entering or activating the brain, may initially trigger plaque formation and start the amyloid cascade rolling. Tanzi is currently carrying out large-scale metagenomic sequencing of post-mortem AD brains, to catalog the microbes that may be initiating amyloid pathology. In 2018, they published back-to-back papers with a group at Mt. Sinai implicating Herpes viruses in triggering plaque pathology in AD. Tanzi and Moir refer to this as the “antimicrobial protection hypothesis” of AD.

In other studies, Tanzi and his trainee, Zhongcong Xie, published several seminal papers providing the first evidence that the widely used general inhalant anesthetic, isoflurane, induces Abeta generation, apoptosis, and neurodegeneration in the mouse brain and post-operative CSF of patients. This has gradually led to a dramatic reduction in the clinical use of isoflurane in the operating room, especially in elderly patients and Alzheimer's patients. With trainee, Lee Goldstein, Tanzi showed how head injury due to a bomb blast or collision causes rapid induction of tangles and gliosis in mice. Now referred to as the “bobblehead” effect, it has been postulated to be the main cause of the subsequent onset of chronic traumatic encephalopathy in human subjects exposed to repeated concussion and head trauma.

Tanzi has testified to Congress on both Alzheimer's disease and most recently, in September 2019, on maintaining brain health. Tanzi serves on dozens of editorial and scientific advisory boards and as chair of the Cure Alzheimer's Fund Research Leadership Group. He has published over 600 research papers and has been issued numerous patents. He has co-authored three international bestsellers with Deepak Chopra. Tanzi has hosted three shows on public television: Super Brain with Rudy Tanzi, Super Genes with Tanzi, and The Brain, Body, Mind Connection. Tanzi regularly appears on network television programs, including CBS Morning News , The Today Show , NBC Nightly News , CNN, MSNBC, Oz, and Nova . [9]

Summary of key discoveries

Music

In musical pursuits, Tanzi serves as a studio keyboard player for Joe Perry and Aerosmith. [1] He also co-wrote the tribute song to Alzheimer's patients called "Remember Me", performed by singer Chris Mann. [10] [11] He plays keyboards on the albums: Aerosmith: Music from Another Dimension by Aerosmith and Joe Perry's Sweetzerland Manifesto. He has also performed with the legendary opera star, Renee Fleming.

Awards and honors

Tanzi has received numerous awards, including the two highest awards for Alzheimer's disease research: The Metlife Foundation Award for Medical Research in Alzheimer's Disease Award and The Potamkin Prize. He was included on the list of the "Harvard 100 Most Influential Alumni", and was chosen by the Geoffrey Beene Foundation as a “Rock Star of Science”. In 2015, he was named by Time to the Timr100 Most Influential People in the World list. In 2015, Tanzi also received the Smithsonian American Ingenuity Award, the nation's highest award for invention and innovation. He also received the Silver Innovator Award, the Brain Research Foundation Award, the Ronald Reagan Award, the Pew Scholar Award, the Nathan Shock Award, the Rustum Roy Award, and the Oneness in Humanity Award.

In 2018, Tanzi was inducted into the Rhode Island Heritage Hall of Fame. He was also inducted into the Cranston Hall of Fame in 2000. Tanzi was awarded an honorary doctorate from The University of Rhode Island on May 17, 2015. [12]

Selected publications

Books

Articles

Related Research Articles

<span class="mw-page-title-main">Amyloid beta</span> Group of peptides

Amyloid beta denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. It is now believed that certain misfolded oligomers can induce other Aβ molecules to also take the misfolded oligomeric form, leading to a chain reaction akin to a prion infection. The oligomers are toxic to nerve cells. The other protein implicated in Alzheimer's disease, tau protein, also forms such prion-like misfolded oligomers, and there is some evidence that misfolded Aβ can induce tau to misfold.

<span class="mw-page-title-main">Amyloid-beta precursor protein</span> Mammalian protein found in humans

Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. It functions as a cell surface receptor and has been implicated as a regulator of synapse formation, neural plasticity, antimicrobial activity, and iron export. It is coded for by the gene APP and regulated by substrate presentation. APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients.

<span class="mw-page-title-main">Amyloid plaques</span> Extracellular deposits of the amyloid beta protein

Amyloid plaques are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. Abnormal neurites in amyloid plaques are tortuous, often swollen axons and dendrites. The neurites contain a variety of organelles and cellular debris, and many of them include characteristic paired helical filaments, the ultrastructural component of neurofibrillary tangles. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve with an average plaque area of 400-450 square micrometers (µm²). The smallest plaques, which often consist of diffuse deposits of Aβ, are particularly numerous. The apparent size of plaques is influenced by the type of stain used to detect them, and by the plane through which they are sectioned for analysis under the microscope. Plaques form when Aβ misfolds and aggregates into oligomers and longer polymers, the latter of which are characteristic of amyloid. Misfolded and aggregated Aβ is thought to be neurotoxic, especially in its oligomeric state.

<span class="mw-page-title-main">Neurodegenerative disease</span> Central nervous system disease

A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

<span class="mw-page-title-main">Beta-secretase 1</span> Enzyme

Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is encoded by the BACE1 gene. Expression of BACE1 is observed mainly in neurons.

The biochemistry of Alzheimer's disease, the most common cause of dementia, is not yet very well understood. Alzheimer's disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain. Amyloid beta is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein amyloid-beta precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of proteolytic complex involved in APP processing and degradation.

<span class="mw-page-title-main">Presenilin</span>

Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset forms of familial Alzheimer's disease by Peter St George-Hyslop. Vertebrates have two presenilin genes, called PSEN1 that codes for presenilin 1 (PS-1) and PSEN2 that codes for presenilin 2 (PS-2). Both genes show conservation between species, with little difference between rat and human presenilins. The nematode worm C. elegans has two genes that resemble the presenilins and appear to be functionally similar, sel-12 and hop-1.

<span class="mw-page-title-main">Presenilin-1</span> Protein-coding gene in the species Homo sapiens

Presenilin-1(PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid-beta precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.

<span class="mw-page-title-main">Alzheimer's disease</span> Progressive neurodegenerative disease

Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens, and is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation, mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years.

Early-onset Alzheimer's disease (EOAD), also called younger-onset Alzheimer's disease (YOAD), is Alzheimer's disease diagnosed before the age of 65. It is an uncommon form of Alzheimer's, accounting for only 5–10% of all Alzheimer's cases. About 60% have a positive family history of Alzheimer's and 13% of them are inherited in an autosomal dominant manner. Most cases of early-onset Alzheimer's share the same traits as the "late-onset" form and are not caused by known genetic mutations. Little is understood about how it starts.

Solanezumab is a monoclonal antibody being investigated by Eli Lilly as a neuroprotector for patients with Alzheimer's disease. The drug originally attracted extensive media coverage proclaiming it a breakthrough, but it has failed to show promise in Phase III trials.

The Alzheimer's disease biomarkers are neurochemical indicators used to assess the risk or presence of the disease. The biomarkers can be used to diagnose Alzheimer's disease (AD) in a very early stage, but they also provide objective and reliable measures of disease progress. It is imperative to diagnose AD disease as soon as possible, because neuropathologic changes of AD precede the symptoms by years. It is well known that amyloid beta (Aβ) is a good indicator of AD disease, which has facilitated doctors to accurately pre-diagnose cases of AD. When Aβ peptide is released by proteolytic cleavage of amyloid-beta precursor protein, some Aβ peptides that are solubilized are detected in CSF and blood plasma which makes AB peptides a promising candidate for biological markers. It has been shown that the amyloid beta biomarker shows 80% or above sensitivity and specificity, in distinguishing AD from dementia. It is believed that amyloid beta as a biomarker will provide a future for diagnosis of AD and eventually treatment of AD.

<span class="mw-page-title-main">P3 peptide</span>

p3 peptide also known as amyloid β- peptide (Aβ)17–40/42 is the peptide resulting from the α- and γ-secretase cleavage from the amyloid precursor protein (APP). It is known to be the major constituent of diffuse plaques observed in Alzheimer's disease (AD) brains and pre-amyloid plaques in people affected by Down syndrome. However, p3 peptide's role in these diseases is not truly known yet.

The ion channel hypothesis of Alzheimer’s disease (AD), also known as the channel hypothesis or the amyloid beta ion channel hypothesis, is a more recent variant of the amyloid hypothesis of AD, which identifies amyloid beta (Aβ) as the underlying cause of neurotoxicity seen in AD. While the traditional formulation of the amyloid hypothesis pinpoints insoluble, fibrillar aggregates of Aβ as the basis of disruption of calcium ion homeostasis and subsequent apoptosis in AD, the ion channel hypothesis in 1993 introduced the possibility of an ion-channel-forming oligomer of soluble, non-fibrillar Aβ as the cytotoxic species allowing unregulated calcium influx into neurons in AD.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by two hallmarks: senile plaques and the neurofibrillary tangle. Senile plaques are extracellular aggregations of amyloid-b (Aβ) protein. Neurofibrillary tangles are collections of hyperphosphorylated tau protein associated with microtubules found within neurons. Senile plaques and neurofibrillary tangles are widespread throughout brain tissue and mirror other pathological changes associated with AD.

Microglia are the primary immune cells of the central nervous system, similar to peripheral macrophages. They respond to pathogens and injury by changing morphology and migrating to the site of infection/injury, where they destroy pathogens and remove damaged cells.

Colin Louis MastersMD is an Australian neuropathologist who researches Alzheimer's disease and other neurodegenerative disorders. He is laureate professor of pathology at the University of Melbourne.

<span class="mw-page-title-main">Experimental models of Alzheimer's disease</span>

Experimental models of Alzheimer's disease are organism or cellular models used in research to investigate biological questions about Alzheimer's disease as well as develop and test novel therapeutic treatments. Alzheimer's disease is a progressive neurodegenerative disorder associated with aging, which occurs both sporadically or due to familial passed mutations in genes associated with Alzheimer's pathology. Common symptoms associated with Alzheimer's disease include: memory loss, confusion, and mood changes.

Alzheimer's disease (AD) in the Hispanic/Latino population is becoming a topic of interest in AD research as Hispanics and Latinos are disproportionately affected by Alzheimer's Disease and underrepresented in clinical research. AD is a neurodegenerative disease, characterized by the presence of amyloid-beta plaques and neurofibrillary tangles, that causes memory loss and cognitive decline in its patients. However, pathology and symptoms have been shown to manifest differently in Hispanic/Latinos, as different neuroinflammatory markers are expressed and cognitive decline is more pronounced. Additionally, there is a large genetic component of AD, with mutations in the amyloid precursor protein (APP), Apolipoprotein E APOE), presenilin 1 (PSEN1), bridging Integrator 1 (BIN1), SORL1, and Clusterin (CLU) genes increasing one's risk to develop the condition. However, research has shown these high-risk genes have a different effect on Hispanics and Latinos then they do in other racial and ethnic groups. Additionally, this population experiences higher rates of comorbidities, that increase their risk of developing AD. Hispanics and Latinos also face socioeconomic and cultural factors, such as low income and a language barrier, that affect their ability to engage in clinical trials and receive proper care.

Alzheimer's disease (AD) in African Americans is becoming a rising topic of interest in AD care, support, and scientific research, as African Americans are disproportionately affected by AD. Recent research on AD has shown that there are clear disparities in the disease among racial groups, with higher prevalence and incidence in African Americans than the overall average. Pathologies for Alzheimer’s also seem to manifest differently in African Americans, including with neuroinflammation markers, cognitive decline, and biomarkers. Although there are genetic risk factors for Alzheimer’s, these account for few cases in all racial groups.

References

  1. 1 2 Fletcher, Bevin (26 Jun 2015). "Alzheimer's Expert Jams with Aerosmith". Drug Discovery & Development . Archived from the original on 27 June 2015.
  2. ↑ Gusella, James F.; Wexler, Nancy S.; Conneally, P. Michael; Naylor, Susan L.; Anderson, Mary Anne; Tanzi, Rudolph E.; Watkins, Paul C.; Ottina, Kathleen; Wallace, Margaret R.; Sakaguchi, Alan Y.; Young, Anne B.; Shoulson, Ira; Bonilla, Ernesto; Martin, Joseph B.; et al. (Gusella, J., Wexler, N., Conneally, P., et al) (1983). "A polymorphic DNA marker genetically linked to Huntington's disease". Nature. 306 (5940): 234–238. Bibcode:1983Natur.306..234G. doi:10.1038/306234a0. PMID   6316146. S2CID   4320711 . Retrieved 13 January 2023.
  3. ↑ Tanzi, R. E.; Petrukhin, K.; Chernov, I.; Pellequer, J. L.; Wasco, W.; Ross, B.; Romano, D. M.; Parano, E.; Pavone, L.; Brzustowicz, L. M. (December 1993). "The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene". Nature Genetics. 5 (4): 344–350. doi:10.1038/ng1293-344. ISSN   1061-4036. PMID   8298641. S2CID   610188.
  4. ↑ Choi SH, Kim YH, Hebisch M, Sliwinski C, Lee S, D'Avanzo C, Chen H, Hooli B, Asselin C, Muffat J, Klee JB, Zhang C, Wainger BJ, Peitz M, Kovacs DM, Woolf CJ, Wagner SL, Tanzi RE, Kim DY (November 13, 2014). "A three-dimensional human neural cell culture model of Alzheimer's disease". Nature . 515 (7526): 274–8. Bibcode:2014Natur.515..274C. doi:10.1038/nature13800. PMC   4366007 . PMID   25307057.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ↑ Torgan, Carol (November 3, 2014). "Human Cells Model Alzheimer's Disease". NIH Research Matters. National Institutes of Health . Retrieved 16 December 2022.
  6. ↑ Christensen, Jen (2013-06-07). "Gene hunter by day, Aerosmith organist by night". CNN. Retrieved 2023-02-14.
  7. 1 2 Tanzi RE, Bertram L (February 25, 2005). "Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective". Cell . 120 (4): 545–55. doi: 10.1016/j.cell.2005.02.008 . PMID   15734686. S2CID   206559875.
  8. ↑ Tanzi RE, Gusella JF, Watkins PC, Bruns GA, St George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL (February 20, 1987). "Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus". Science . 235 (4791): 880–4. Bibcode:1987Sci...235..880T. doi:10.1126/science.2949367. PMID   2949367 . Retrieved 1 January 2023.
  9. ↑ Nanos, Janelle (2017-10-13). "Forging a better connection between the brain and the mind". The Boston Globe. Retrieved 2017-10-16.
  10. ↑ Chris Mann (2015-01-22). "Chris Mann - Remember Me (An Anthem for Alzheimer's Disease)". YouTube. Retrieved 2017-10-16.
  11. ↑ Tanzi, Rudy; Mann, Chris (2017-03-03). "Curing Alzheimer's with Science and Song". TEDxNatick. Retrieved 2017-10-16.
  12. ↑ Staff. "Brain scientist "rock star" to address class of 2015". University of Rhode Island. Archived from the original on 11 April 2015. Retrieved 26 Jun 2015.
  13. ↑ Decoding darkness : the search for the genetic causes of Alzheimer's disease (Book, 2000). OCLC   45226067.
  14. ↑ Super brain: unleashing the explosive power of your mind to maximize health, happiness, and spiritual well-being (Book, 2012). OCLC   810953657.
  15. ↑ Chopra, Deepak; Tanzi, Rudolph (2015). Super Genes: The hidden key to total well-being. OCLC   1001632172 – via worldcat.org.
  16. ↑ The Healing Self: A Revolutionary New Plan to Supercharge Your Immunity and Stay Well for Life (Book, 2018). OCLC   1024080343 . Retrieved 3 May 2018– via WorldCat.
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