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Dr. Todd Golde

Therapeutic Approaches to Neurodegenerative Disease

Dr. Todd GoldeDirector, CTRND;
Director, 1Florida ADRC;
Professor, Neuroscience;
Investigator, McKnight Brain Institute and CTRND

Residency, Clinical Pathology and Laboratory Medicine, University of Pennsylvania, 1994-1996
Post Doc, Institute of Pathology, Case Western Reserve University, 1990-1992
MD, Medicine, Case Western Reserve University, 1994
Ph.D., Pathology, Case Western Reserve University, 1991
B.A., Biology/Immunology, Amherst College, 1985



Contact Dr. Golde
Phone: 352-273-9458 (Administrative Assistant Pat)

For undergraduates wishing to volunteer. Send an email to Pat Joy ( with “Possible Undergrad Volunteer” in the subject line. Please provide a brief background of your interest in the Golde laboratory, your research experience to date, your current GPA, number of hours you could commit per week, and your future plans (Med School, Grad School etc…). Dr. Golde will review these requests and contact you for a meeting if we have slots available.

Research Focus
Dr. Golde’s laboratory conduct’s disease oriented research with a specific, but not exclusive, focus on neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson Disease (PD). Our basic road map for this research is to try and understand the disease, create models that mimic aspects of the disease process in a time course that is amenable to study, identify targets for intervention, and opportunistically develop and evaluate therapies that might alter the disease course. We are highly collaborative laboratory and believe in leveraging our infrastructure with respect to disease models, knowledge, and technologies to help others move their research forward.


1Florida Alzheimer’s Disease Research Center


1Florida Alzheimer’s Disease Research Center. Dr. Golde directs the 1Florida ADRC for more information on the ADRC please use the link The 1Florida is a consortium of Florida institutions helping to change the current understanding of Alzheimer’s disease and related dementias from being incurable, inevitable and largely untreatable to a new reality in which these diseases are curable, preventable and treatable. Funded by the NIH P50 AG047266.



Current Projects in the Golde Lab.


  1. Somatic transgenesis and AAV based models of Neurodegeneration (Yona Levites, PhD, Carolina Ceballos-Diaz, Pedro Cruz, Awilda Rosario and Paramita Chakrabarty PhD). We have developed a method using recombinant adenoassociated viral vectors (rAAV) to transduce large portions of the neonatal mouse brain and spinal cord. We refer to this technique as r somatic brain or spinal cord transgenesis. Using this technique we can much more rapidly model various aspects of neurodegenerative disease for a fraction of the costs associated with traditional transgenic modeling. We have established over a dozen collaborations based on this technique. We welcome collaborations and are also willing to provide training in this methodology. We continue to refine this methodology and develop new combinations of vectors and capsids to selectively transduce various cell types in the brain, periphery, and in culture. This technology supports many of our funded projects.


Selected Publications

Chakrabarty P, Rosario A, Cruz P, Siemienski Z, Ceballos-Diaz C, Crosby K, Jansen K, Borchelt DR, Kim JY, Jankowsky JL, Golde TE, Levites Y. Capsid serotype and timing of injection determines AAV transduction in the neonatal mice brain. PloS one. 2013;8(6):e67680. PMCID: 3692458.

Levites Y, Jansen K, Smithson LA, Dakin R, Holloway VM, Das P, Golde TE. Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid beta, amyloid beta40, and amyloid beta42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(46):11923-8.


  1. A Systems Approach to Understand and Therapeutically Target Innate Immunity in Neurodegenerative Disease (Paramita Chakrabarty PhD, Brenda Moore PhD, Chris Janus PhD, Yona Levites, PhD, Carolina Ceballos-Diaz, Pedro Cruz, Awilda Rosario and Paramita Chakrabarty PhD) Altered central nervous system (CNS) proteostasis, characterized by accumulation of extracellular or intracellular proteinaceous deposits, is thought to be a key trigger of many neurodegenerative disorders. There is considerable evidence that various assemblies of the aggregated proteins that form these inclusions can activate the innate immune system which, in turn, can contribute to the degenerative cascade. There is also growing evidence that alterations in innate immune signaling can play a key role in regulating proteostasis of key pathogenic proteins linked to neurodegenerative disorders. We term this complex interplay between the innate immune system and proteinopathy, immunoproteostasis. In a contextually dependent fashion, immunoproteostasis can have positive or negative effects on the proteinopathy and degenerative phenotype. Because of these effects and the plethora of therapeutic targets in the innate immune system, there is considerable interest in manipulating immunoproteostasis for potential disease modification in neurodegenerative diseases. We are currently combing systems level analysis, modeling and cell culture studies to understand the role of innate immunity in various neurodegenerative disorders. Our work on Alzheimer’s disease is funded by the NIH U01 AG046139. This is collaborative multi-institution grant funded by NIH’s accelerating medicine partnership (AMP) program. Collaborators include Dr. Nilufer Ertekin-Taner, Dennis Dickson and Steve Younkin at Mayo Clinic Florida and Nathan Price, Cory Funk and HongDong Li at Institute for Stems Biology in Seattle.


Selected Publications


Chakrabarty P, Li A, Ceballos-Diaz C, Eddy JA, Funk CC, Moore B, DiNunno N, Rosario AM, Cruz PE, Verbeeck C, Sacino A, Nix S, Janus C, Price ND, Das P, Golde TE. IL-10 Alters Immunoproteostasis in APP Mice, Increasing Plaque Burden and Worsening Cognitive Behavior. Neuron. 2015;85(3):519-33. PMCID: 4320003.

Chakrabarty P, Jansen-West K, Beccard A, Ceballos-Diaz C, Levites Y, Verbeeck C, Zubair AC, Dickson D, Golde TE, Das P. Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2010;24(2):548-59. PMCID: 3083918.

Chakrabarty, P., L. Tianbai, A. Herring, C. Ceballos-Diaz, P. Das, and T.E. Golde, Hippocampal expression of murine IL-4 results in exacerbation of amyloid deposition. Mol Neurodegener, 2012. 7: p. 36.

Chakrabarty, P., C. Ceballos-Diaz, A. Beccard, C. Janus, D. Dickson, T.E. Golde, and P. Das, IFN-gamma promotes complement expression and attenuates amyloid plaque deposition in amyloid beta precursor protein transgenic mice. J Immunol, 2010. 184(9): p. 5333-43.

Chakrabarty, P., C. Ceballos-Diaz, W.L. Lin, A. Beccard, K. Jansen-West, N.R. McFarland, C. Janus, D. Dickson, P. Das, and T.E. Golde, Interferon-gamma induces progressive nigrostriatal degeneration and basal ganglia calcification. Nat Neurosci, 2011. 14(6): p. 694-6.

Ayers, J.I., S. Fromholt, O. Sinyavskaya, Z. Siemienski, A.M. Rosario, A. Li, K.W. Crosby, P.E. Cruz, N.M. DiNunno, C. Janus, C. Ceballos-Diaz, D.R. Borchelt, T.E. Golde, P. Chakrabarty, and Y. Levites, Widespread and efficient transduction of spinal cord and brain following neonatal AAV injection and potential disease modifying effect in ALS mice. Mol Ther, 2015. 23(1): p. 53-62.


  1. Recombinant Antibody and Vaccine approaches for Alzheimer’s disease and other amyloid disease (Yona Levites, PhD, Brenda Moore PhD, Pedro Cruz PhD). Aggregation and accumulation of the amyloid β protein in the brain is thought to trigger a complex degenerative cascade that results in Alzheimer’s disease. These studies build on ~15 years of research in the laboratory and are designed to develop novel active and passive immunotherapies that safely and effectively target Aβ amyloid in AD. More recently we are now focusing on immunotherapies for tau and alpha-synuclein. Notably these therapies may have benefit in other amyloid diseases. In particular we are focusing on using rAAV –vectors to deliver optimized functional recombinant antibodies directly to the brain and developing conformation vaccines against misfolded proteins. We are also more systematically evaluating the pharmacokinetics and brain exposure of peripheral delivered antibodies, as well as how altered innate immune activation alters efficacy of these immunotherapies Funded by NIH Grant AG18454 and the BrightFocus Foundation (Y. Levites PI).


Selected Publications


Levites Y, Smithson LA, Price RW, Dakin RS, Yuan B, Sierks MR, Kim J, McGowan E, Reed DK, Rosenberry TL, Das P, Golde TE. Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer’s disease mouse models. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2006;20(14):2576-8.

Levites Y, Jansen K, Smithson LA, Dakin R, Holloway VM, Das P, Golde TE. Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid beta, amyloid beta40, and amyloid beta42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(46):11923-8.

Levites Y, Das P, Price RW, Rochette MJ, Kostura LA, McGowan EM, Murphy MP, Golde TE. Anti-Abeta42- and anti-Abeta40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model. The Journal of clinical investigation. 2006;116(1):193-201. PMCID: 1307561.

Das P, Howard V, Loosbrock N, Dickson D, Murphy MP, Golde TE. Amyloid-beta immunization effectively reduces amyloid deposition in FcRgamma-/- knock-out mice. The Journal of Neuroscience: the official journal of the Society for Neuroscience. 2003;23(24):8532-8


  1. Gamma-Secretase Modulators and the role of short amyloid peptides in Alzheimer’s disease. (Thomas Ladd, Christian Lessard, PhD, Yong Ran PhD, Carolina Hernandez, Brenda Moore PhD). A longer species of Aβ, Aβ42, is thought to be the key pathogenic molecular in AD. It is critical for deposition of Aβ. Thus, lowering levels of Aβ42 could have a major impact on the development of AD. In collaboration with Dr. Edward Koo’s laboratory (UCSD), we previously demonstrated that select drug and drug-like compounds could modulate Aβ42 production and that this effect was attributable to direct alteration of γ-secretase activity. Drug with this type of effect on Aβ are now referred to as a γ-secretase modulators (GSMs). These studies provided the rationale for clinical testing of GSMs by the commercial sector. Our current studies focus on 1) the biological properties of short Aβ (in collaboration with Drs. Diego-Rincon, and Fernandez-Funez) and 2) identifying new GSMs from natural products (collaboration with Dr. Ihklas Kah, U. Miss, and Amy Wright, FAU). Previously funded by NIH AG20206; current funding from the Karen L. Wren Foundation.


Selected Publications


Jung JI, Ladd TB, Kukar T, Price AR, Moore BD, Koo EH, Golde TE*, Felsenstein KM*. Steroids as gamma-secretase modulators. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2013;27(9):3775-85. PMCID: 3752532. *Co-corresponding authors

Kukar T, Murphy MP, Eriksen JL, Sagi SA, Weggen S, Smith TE, Ladd T, Khan MA, Kache R, Beard J, Dodson M, Merit S, Ozols VV, Anastasiadis PZ, Das P, Fauq A, Koo EH, Golde TE. Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production. Nature medicine. 2005;11(5):545-50.

Eriksen JL, Sagi SA, Smith TE, Weggen S, Das P, McLendon DC, Ozols VV, Jessing KW, Zavitz KH, Koo EH, Golde TE. NSAIDs and enantiomers of flurbiprofen target gamma-secretase and lower Abeta 42 in vivo. The Journal of clinical investigation. 2003;112(3):440-9. PMCID: 166298.

Weggen S, Eriksen JL, Das P, Sagi SA, Wang R, Pietrzik CU, Findlay KA, Smith TE, Murphy MP, Bulter T, Kang DE, Marquez-Sterling N, Golde TE, Koo EH. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature. 2001;414(6860):212-6.



  1. Therapeutic Targeting of Intramembrane Cleaving Protease. (Yong Ran PhD, Christian Lessard). Presenilin is the catalytic component of a multisubunit protease called γ-secretase that cleaves membrane proteins within their transmembrane domains. γ-Secretase cleaves a number of proteins and mediates signal transduction by many of these. In 2003, in collaboration with Dr. Chris Ponting, we identified a family of intramembrane proteases (signal peptide peptidases) that were related to γ-secretase. We are evaluating targeting these proteases in cancer, immunologic disease, and malaria. These studies are currently being conducted in collaboration with Dr. Barbara Osborne UMASS Amherst and Dr. Lucio Miele Tulane. Currently the studies are focused on understanding how γ-secretase inhibitors currently in trial for cancer mediate their anti-tumor effects and if these inhibitors are biologically equivalent. Funded by the NIH 1P01CA166009 01A1 .


Selected Publications


Ponting CP, Hutton M, Nyborg A, Baker M, Jansen K, Golde TE. Identification of a novel family of presenilin homologues. Human molecular genetics. 2002;11(9):1037-44.

Roderick JE, Gonzalez-Perez G, Kuksin CA, Dongre A, Roberts ER, Srinivasan J, Andrzejewski C, Jr., Fauq AH, Golde TE, Miele L, Minter LM. Therapeutic targeting of NOTCH signaling ameliorates immune-mediated bone marrow failure of aplastic anemia. The Journal of experimental medicine. 2013;210(7):1311-29. doi: 10.1084/jem.20112615. PubMed PMID: 23733784; PubMed Central PMCID: PMC3698520.

Ran Y, Ladd GZ, Ceballos-Diaz C, Jung JI, Greenbaum D, Felsenstein KM, Golde TE. Differential Inhibition of Signal Peptide Peptidase Family Members by Established gamma-Secretase Inhibitors. PloS one. 2015;10(6):e0128619. doi: 10.1371/journal.pone.0128619. PubMed PMID: 26046535; PubMed Central PMCID: PMC4457840.

Harbut MB, Patel BA, Yeung BK, McNamara CW, Bright AT, Ballard J, Supek F, Golde TE, Winzeler EA, Diagana TT, Greenbaum DC. Targeting the ERAD pathway via inhibition of signal peptide peptidase for antiparasitic therapeutic design. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(52):21486-91. PMCID: 3535666.


  1. Spreading of Pathology. In collaborative studies led by Dr. Benoit Giassion ( we have been examining how pathologies spread in the CNS. Our data suggest that both prion like and other mechanism contribute to the spread of pathology.


Selected Publications


Sacino, A.N., J.I. Ayers, M.M. Brooks, P. Chakrabarty, V.J. Hudson, 3rd, J.K. Howard, T.E. Golde, B.I. Giasson, and D.R. Borchelt, Non-prion-type transmission in A53T alpha-synuclein transgenic mice: a normal component of spinal homogenates from naive non-transgenic mice induces robust alpha-synuclein pathology. Acta Neuropathol, 2016. 131(1): p. 151-4.

Sacino, A.N., M. Brooks, M.A. Thomas, A.B. McKinney, N.H. McGarvey, N.J. Rutherford, C. Ceballos-Diaz, J. Robertson, T.E. Golde, and B.I. Giasson, Amyloidogenic alpha-synuclein seeds do not invariably induce rapid, widespread pathology in mice. Acta Neuropathol, 2014. 127(5): p. 645-65.

Sacino, A.N., M. Brooks, M.A. Thomas, A.B. McKinney, S. Lee, R.W. Regenhardt, N.H. McGarvey, J.I. Ayers, L. Notterpek, D.R. Borchelt, T.E. Golde, and B.I. Giasson, Intramuscular injection of alpha-synuclein induces CNS alpha-synuclein pathology and a rapid-onset motor phenotype in transgenic mice. Proc Natl Acad Sci U S A, 2014. 111(29): p. 10732-7.

Sacino, A.N., M. Brooks, A.B. McKinney, M.A. Thomas, G. Shaw, T.E. Golde, and B.I. Giasson, Brain injection of alpha-synuclein induces multiple proteinopathies, gliosis, and a neuronal injury marker. J Neurosci, 2014. 34(37): p. 12368-78.

Sacino, A.N., M.A. Thomas, C. Ceballos-Diaz, P.E. Cruz, A.M. Rosario, J. Lewis, B.I. Giasson, and T.E. Golde, Conformational templating of alpha-synuclein aggregates in neuronal-glial cultures. Mol Neurodegener, 2013. 8: p. 17.

Golde, T.E., D.R. Borchelt, B.I. Giasson, and J. Lewis, Thinking laterally about neurodegenerative proteinopathies. J Clin Invest, 2013. 123(5): p. 1847-55.


  1. New Initiatives. Despite reasonable consensus in the field that the key triggering events in AD are the development of the Aβ and tau proteinopathies, there is considerable uncertainty as to how these proteinopathies lead to brain organ failure. Perhaps one of the biggest challenges the field faces for developing novel therapies that would work in symptomatic patients is understanding the pathobiological processes that follow the triggering proteinopathies. We simply do not have sufficient biologic insight into what processes we may want to target. Our lab is currently evaluating ways to target multiple downstream pathways using combination therapies based on rAAV mediated delivery of biologic agents and gene editing technologies. In addition we are also exploring whether there are novel targets in the cellular stress response pathways that can have a broad effect on AD pathologies.


Selected Publications


Park, H.J., Y. Ran, J.I. Jung, O. Holmes, A.R. Price, L. Smithson, C. Ceballos-Diaz, C. Han, M.S. Wolfe, Y. Daaka, A.E. Ryabinin, S.H. Kim, R.L. Hauger, T.E. Golde, and K.M. Felsenstein, The stress response neuropeptide CRF increases amyloid-beta production by regulating gamma-secretase activity. EMBO J, 2015. 34(12): p. 1674-86.


Join the team!

We are always looking for talented Postdocs to join our team. Please contact Dr. Golde to see if positons are available.


Links to current NIH Grants.


Publications on PubMed


General Reviews

Golde, T.E., D.R. Borchelt, B.I. Giasson, and J. Lewis, Thinking laterally about neurodegenerative proteinopathies. J Clin Invest, 2013. 123(5): p. 1847-55.

Golde, T.E., L.S. Schneider, and E.H. Koo, Anti-abeta therapeutics in Alzheimer’s disease: the need for a paradigm shift. Neuron, 2011. 69(2): p. 203-13.

Golde, T.E., B.T. Lamb, and D. Galasko, Right sizing funding for Alzheimer’s disease. Alzheimers Res Ther, 2011. 3(3): p. 17.

Golde, T.E., E.H. Koo, K.M. Felsenstein, B.A. Osborne, and L. Miele, gamma-Secretase inhibitors and modulators. Biochim Biophys Acta, 2013. 1828(12): p. 2898-907