Todd E Golde,
Professor, Director McKnight Brain Institute
About Todd E Golde
Todd E. Golde, M.D., Ph.D., is director of the Evelyn F. and William L. McKnight Brain Institute (MBI) of the University of Florida, where he oversees, champions and facilitates neuroscience and neuromedicine research programs across the UF campus. A professor of neuroscience and neurology, Dr. Golde joined the UF faculty in 2009 and became founding director of UF’s Center for Translational Research in Neurodegenerative Disease (CTRND), which he led until taking the helm at the MBI in December 2016.
An internationally known expert in the scientific understanding of Alzheimer’s disease (AD), Dr. Golde has published more than 290 papers that have been cited more than 36,000 times. Over time his research has taken on a more transnational focus. He currently directs i) the NIH funded 1Florida Alzheimer’s Disease Research Center (ADRC, https://1floridaadrc.org/) that focuses on early detection and markers of progression in in diverse populations (especially Hispanics an African Americans) ii) a consortium U01 under the NIH’s accelerating medicine partnership AD program (AMP-AD) designed to identify novel targets in the immune systems in AD iii) studies exploring a novel immunotherapy targeting the HPA axis in AD , iv) the use of a novel brain slice culture model of tauopathy and α-synucleinopathy to identify therapeutic targets for the proteinopathies and the dysfunction that they cause, and v) an gene therapy approach to treating trigmenal neuralgia. Underlying his laboratory’s wet-bench research studies is the development of an extensive rAAV vector “toolkit” that enables us to accelerate translational preclinical studies that can help advance therapeutic discovery in many disease settings.
In addition to his research and intramural administrative activities, in recent years Dr. Golde has been an active advocate for AD and neurodegenerative disease research at the state, national and international levels. At the national level, he has served on the medical and scientific advisory board for the National Alzheimer’s Association and he continue to do so for the Bright Focus Foundation. At the state level, he has served on several advisory boards relating to AD, and has worked to secure state support for Alzheimer’s research at UF as well as implement a statewide grants program to support AD research. Through his scientific reviews and presentations at national and international conferences, he not only discuss scientific advances, but also highlight the many challenges that we face in combating the AD epidemic (see, for example, Golde et al Alz Res & Therapy 2011, Golde et al Neuron 2011, Golde J. Neurochemistry 2016, Golde et al. Science 2018, Dawson et al Nature Neuroscience 2018, Golde, Neuron 2019).
Accomplishments
Director of the Evelyn F. and William L. McKnight Brain Institute
2017-current
·
University of Florida
Alzheimer's Research UK Drug Discovery Institutes Advisory board
2016-current
·
ARUK
Co-Organizer EMBO Conferences on Neurodegenerative disease
2015-2017
·
EMBO
Faculty Research Award Basic Science
2014
·
UF College of Medicine
Medical and Scientific Advisory Council for the National Alzheimer’s Association
2012-2019
·
National Alzheimer's Assocaition
Purple Ribbon Task Force for Alzheimer’s Disease
2012-2013
·
Florida Speaker of the House of Representatives Appointment
Alzheimer’s Disease Advisory Committee (ADI)
2010-2016
·
State of Florida, Department of Elder Affairs, Governor's Appointment
Founding Director, Center for Translational Research in Neurodegenerative disease
2010-2016
·
University of Florida
Met Life Award for Medical Research
2010
·
Met Life Foundation
Stephen DeArmond Lecturer
2010
·
American Association of Neuropathology
Thome Award in Alzheimer's Disease Drug Discovery Research
2010
·
Edward N. and Della L. Thome Memorial Foundation
Founding Co-Editor in Chief – Alzheimer’s Research and Therapy
2009-2019
·
BMC
Consulting Editor – Journal of Clinical Investigator
2007-Current
·
American Society for Clinical Investigation
Coins for Alzheimer's Research Trust
2007
·
Rotary Clubs of America
BrightFocus Foundation Alzheimer’s Advisory Board
2006-Current
·
BrightFocus Foundation
Chair , Department of Neuroscience
2003-2009
·
Mayo Clinic Florida
Outstanding Contributor, Alzheimer’s Research Forum
2001
·
Alzheimer's Research Forum
Graduate Education Coordinator, Mayo Clinic Florida
1999-2003
·
Mayo Clinic
Ellison Medical Foundation New Scholar
1998
·
Ellison Medical Foundation
Paul Beeson Physician Faculty Scholar
1997
·
American Federation for Aging Research
Zenith Award
1995
·
Alzheimer’s Association
Experimental Pathologist-in-Training Award
1993
·
American Society for Investigative Pathology
The Oscar E. Schotte Award, Awarded to a senior student for the outstanding Honor's thesis in the Department of Biology.
1985
·
Amherst College
Research Profile
CONTRIBUTIONS TO SCIENCE 1. As a MD PhD student and postdoc with Dr. Steven Younkin, I played a pivotal role in studies showing that the amyloid beta protein (Abeta) was a normal metabolite and that mutations that cause AD alter Abeta production in a manner that promote Abeta aggregation. These studies provided pivotal support for the Abeta aggregate (amyloid) hypothesis of AD and enabled drug discovery programs aimed at altering Abeta accumulation. a) Golde TE, Estus S, Younkin LH, Selkoe DJ, Younkin SG. Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. Science. 1992;255(5045):728-30. doi: 10.1126/science.1738847. PubMed PMID: 1738847. b) Shoji M*, Golde TE*, Ghiso J, Cheung TT, Estus S, Shaffer LM, Cai XD, McKay DM, Tintner R, Frangione B. Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science. 1992;258(5079):126-9. doi: 10.1126/science.1439760. PubMed PMID: 1439760.. c) Cai XD, Golde TE, Younkin SG. Release of excess amyloid beta protein from a mutant amyloid beta protein precursor. Science. 1993;259(5094):514-6. doi: 10.1126/science.8424174. PubMed PMID: 8424174. d) Suzuki N, Cheung TT, Cai XD, Odaka A, Otvos L, Eckman C, Golde TE, Younkin SG. An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science. 1994;264(5163):1336-40. doi: 10.1126/science.8191290. PubMed PMID: 8191290. 2. In studies conducted in collaboration with Dr. Edward Koo’s laboratory (UCSD), we demonstrated that select non-steroidal anti-inflammatory agents (NSAIDs) could modulate Abeta42 production and that this effect was attributable to direct alteration of gamma-secretase activity. Subsequently we identified compounds that lowered Abeta42 but lacked cyclooxygenase activity, we also described compounds with the opposite effect that raise Aβ42 levels, and finally that these compounds work in part by targeting substrate. These data and modeling studies on the biological properties of “short” Aβ peptides has supported the rationale for development and testing of what are now referred to as gamma-secretase modulators (GSMs) as potential therapeutics for AD. a) 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. doi: 10.1038/35102591. PubMed PMID: 11700559. b) 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. Nat Med. 2005;11(5):545-50. Epub 2005/04/17. doi: 10.1038/nm1235. PubMed PMID: 15834426. c) Kukar TL, Ladd TB, Bann MA, Fraering PC, Narlawar R, Maharvi GM, Healy B, Chapman R, Welzel AT, Price RW, Moore B, Rangachari V, Cusack B, Eriksen J, Jansen-West K, Verbeeck C, Yager D, Eckman C, Ye W, Sagi S, Cottrell BA, Torpey J, Rosenberry TL, Fauq A, Wolfe MS, Schmidt B, Walsh DM, Koo EH, Golde TE. Substrate-targeting gamma-secretase modulators. Nature. 2008;453(7197):925-9. doi: 10.1038/nature07055. PubMed PMID: 18548070; PMCID: PMC2678541. d) Moore BD, Martin J, de Mena L, Sanchez J, Cruz PE, Ceballos-Diaz C, Ladd TB, Ran Y, Levites Y, Kukar TL, Kurian JJ, McKenna R, Koo EH, Borchelt DR, Janus C, Rincon-Limas D, Fernandez-Funez P, Golde TE. Short Aβ peptides attenuate Aβ42 toxicity in vivo. J Exp Med. 2018;215(1):283-301. Epub 2017/12/05. doi: 10.1084/jem.20170600. PubMed PMID: 29208777; PMCID: PMC5748850.3. 3. A parallel area of interest to GSMs has been the therapeutic utility of targeting intramembrane cleaving proteases in a variety of indications. In 2002, in collaboration with Dr. Chris Ponting, we identified a family of intramembrane protease (presenilin homologs/signal peptide peptidases) that was related to gamma-secretase. In work conducted in collaboration with Drs. Osborne (UMASS), Miele (LSU/Tulane), and Greenbaum (U Penn), we have evaluated targeting these proteases in cancer, immunologic disease, and malaria. a) Ponting CP, Hutton M, Nyborg A, Baker M, Jansen K, Golde TE. Identification of a novel family of presenilin homologues. Hum Mol Genet. 2002;11(9):1037-44. doi: 10.1093/hmg/11.9.1037. PubMed PMID: 11978763. b) Das P, Verbeeck C, Minter L, Chakrabarty P, Felsenstein K, Kukar T, Maharvi G, Fauq A, Osborne BA, Golde TE. Transient pharmacologic lowering of Aβ production prior to deposition results in sustained reduction of amyloid plaque pathology. Mol Neurodegener. 2012;7:39. Epub 2012/08/14. doi: 10.1186/1750-1326-7-39. PubMed PMID: 22892055; PMCID: PMC3477045. c) R 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. Proc Natl Acad Sci U S A. 2012;109(52):21486-91. Epub 2012/12/11. doi: 10.1073/pnas.1216016110. PubMed PMID: 23236186; PMCID: PMC3535666. d) Ran Y, Hossain F, Pannuti A, Lessard CB, Ladd GZ, Jung JI, Minter LM, Osborne BA, Miele L, Golde TE. γ-Secretase inhibitors in cancer clinical trials are pharmacologically and functionally distinct. EMBO Mol Med. 2017;9(7):950-66. doi: 10.15252/emmm.201607265. PubMed PMID: 28539479; PMCID: PMC5494507. 4. My laboratory has been at the forefront of developing rAAV-based models and delivery of biotherapeutics to the brain, spinal cord and muscle. Much of this work has focused on delivery of potentially biotherapeutic molecules to models of Alzheimer’s disease. We continue to revise and update this technology, and our most recent study describes using minimally purified rAAV for both in vitro and ex vivo studies, which will enable rAAV technology to be much more accessible to the wider community. a) 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. J Neurosci. 2006;26(46):11923-8. doi: 10.1523/JNEUROSCI.2795-06.2006. PubMed PMID: 17108166; PMCID: PMC6674861. b) 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. Epub 2013/06/25. doi: 10.1371/journal.pone.0067680. PubMed PMID: 23825679; PMCID: PMC3692458. c) Ayers JI, Fromholt S, Sinyavskaya O, Siemienski Z, Rosario AM, Li A, Crosby KW, Cruz PE, DiNunno NM, Janus C, Ceballos-Diaz C, Borchelt DR, Golde TE, Chakrabarty P, Levites Y. 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):53-62. Epub 2014/09/17. doi: 10.1038/mt.2014.180. PubMed PMID: 25228069; PMCID: PMC4426802. d) Goodwin MS, Croft CL, Futch HS, Ryu D, Ceballos-Diaz C, Liu X, Paterno G, Mejia C, Deng D, Menezes K, Londono L, Arjona K, Parianos M, Truong V, Rostonics E, Hernandez A, Boye SL, Boye SE, Levites Y, Cruz PE, Golde TE. Utilizing minimally purified secreted rAAV for rapid and cost-effective manipulation of gene expression in the CNS. Mol Neurodegener. 2020;15(1):15. Epub 2020/03/02. doi: 10.1186/s13024-020-00361-z. PubMed PMID: 32122372; PMCID: PMC7053119. 5. Over the last 10 years, my research has expanded into the area of innate immunity’s role in neurodegenerative disease. Recent work from my lab has challenged a long-standing hypothesis that inflammatory processes in AD accelerate Aβ deposition. Published studies also reveal a potential novel role of interferon-gamma in nigrostriatal degeneration and novel roles for decoy receptors in AD. We have now expanded these studies to broadly explore immune modulators as mediators of neurodegenerative pathways. a) 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 J. 2010;24(2):548-59. Epub 2009/10/13. doi: 10.1096/fj.09-141754. PubMed PMID: 19825975; PMCID: PMC3083918. b) Chakrabarty P, Ceballos-Diaz C, Lin WL, Beccard A, Jansen-West K, McFarland NR, Janus C, Dickson D, Das P, Golde TE. Interferon-γ induces progressive nigrostriatal degeneration and basal ganglia calcification. Nat Neurosci. 2011;14(6):694-6. Epub 2011/05/15. doi: 10.1038/nn.2829. PubMed PMID: 21572432; PMCID: PMC3780582. c) Chakrabarty P, Li A, Ladd TB, Strickland MR, Koller EJ, Burgess JD, Funk CC, Cruz PE, Allen M, Yaroshenko M, Wang X, Younkin C, Reddy J, Lohrer B, Mehrke L, Moore BD, Liu X, Ceballos-Diaz C, Rosario AM, Medway C, Janus C, Li HD, Dickson DW, Giasson BI, Price ND, Younkin SG, Ertekin-Taner N, Golde TE. TLR5 decoy receptor as a novel anti-amyloid therapeutic for Alzheimer’s disease. J Exp Med. 2018;215(9):2247-64. doi: 10.1084/jem.20180484. PubMed PMID: 30158114; PMCID: PMC6122970. d) 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. Epub 2015/01/22. doi: 10.1016/j.neuron.2014.11.020. PubMed PMID: 25619653; PMCID: PMC4320003.
Open Researcher and Contributor ID (ORCID)
0000-0003-1867-7071
Areas of Interest
- Adeno-Associated Viral Gene Therapy
- Alzheimer’s Disease
- Cancer Therapeutics
- Dementia
- Immunoproteostasis
- Neurodegenerative diseases
- Neuroimmune interactions in Neurodegenerative diseases
- Trigeminal Neuralgia
- intramembrane cleaving proteases
Publications
2021
Anti-tau scFvs Targeted to the Cytoplasm or Secretory Pathway Variably Modify Pathology and Neurodegenerative Phenotypes.
Molecular therapy : the journal of the American Society of Gene Therapy.
29(2):859-872
[DOI] 10.1016/j.ymthe.2020.10.007.
[PMID] 33128896.
2021
Il-10 signaling reduces survival in mouse models of synucleinopathy.
NPJ Parkinson's disease.
7(1)
[DOI] 10.1038/s41531-021-00169-8.
[PMID] 33741985.
2021
Integrative functional genomic analysis of intron retention in human and mouse brain with Alzheimer’s disease.
Alzheimer's & dementia : the journal of the Alzheimer's Association.
[DOI] 10.1002/alz.12254.
[PMID] 33480174.
2021
Modulating innate immune activation states impacts the efficacy of specific Aβ immunotherapy.
Molecular neurodegeneration.
16(1)
[DOI] 10.1186/s13024-021-00453-4.
[PMID] 33957936.
2021
Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel: A Meta-analysis.
JAMA neurology.
78(1):102-113
[DOI] 10.1001/jamaneurol.2020.3536.
[PMID] 33074286.
2021
Photodynamic studies reveal rapid formation and appreciable turnover of tau inclusions.
Acta neuropathologica.
141(3):359-381
[DOI] 10.1007/s00401-021-02264-9.
[PMID] 33496840.
2021
Precision therapeutic targets for COVID-19.
Virology journal.
18(1)
[DOI] 10.1186/s12985-021-01526-y.
[PMID] 33781287.
2021
Soluble α-synuclein-antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia.
Proceedings of the National Academy of Sciences of the United States of America.
118(15)
[DOI] 10.1073/pnas.2025847118.
[PMID] 33833060.
2021
Targeting Notch in oncology: the path forward.
Nature reviews. Drug discovery.
20(2):125-144
[DOI] 10.1038/s41573-020-00091-3.
[PMID] 33293690.
2021
Utility of Plasma Neurofilament Light in the 1Florida Alzheimer’s Disease Research Center (ADRC).
Journal of Alzheimer's disease : JAD.
79(1):59-70
[DOI] 10.3233/JAD-200901.
[PMID] 33216030.
2020
Atlas of Transcription Factor Binding Sites from ENCODE DNase Hypersensitivity Data across 27 Tissue Types
Cell Reports.
32(7)
[DOI] 10.1016/j.celrep.2020.108029.
[PMID] 32814038.
2020
Aß40 displays amyloidogenic properties in the non-transgenic mouse brain but does not exacerbate Aß42 toxicity in Drosophila.
Alzheimer's research & therapy.
12(1)
[DOI] 10.1186/s13195-020-00698-z.
[PMID] 33069251.
2020
CD28 Signaling Drives Notch Ligand Expression on CD4 T Cells.
Frontiers in immunology.
11
[DOI] 10.3389/fimmu.2020.00735.
[PMID] 32457739.
2020
Diffusion magnetic resonance imaging-derived free water detects neurodegenerative pattern induced by interferon-γ.
Brain structure & function.
225(1):427-439
[DOI] 10.1007/s00429-019-02017-1.
[PMID] 31894407.
2020
Diversity in Aβ deposit morphology and secondary proteome insolubility across models of Alzheimer-type amyloidosis.
Acta neuropathologica communications.
8(1)
[DOI] 10.1186/s40478-020-00911-y.
[PMID] 32252825.
2020
Do infections have a role in the pathogenesis of Alzheimer disease?
Nature reviews. Neurology.
16(4):193-197
[DOI] 10.1038/s41582-020-0323-9.
[PMID] 32152461.
2020
Fyn depletion ameliorates tauP301L-induced neuropathology.
Acta neuropathologica communications.
8(1)
[DOI] 10.1186/s40478-020-00979-6.
[PMID] 32665013.
2020
Intracerebral Expression of AAV-APOE4 Is Not Sufficient to Alter Tau Burden in Two Distinct Models of Tauopathy.
Molecular neurobiology.
57(4):1986-2001
[DOI] 10.1007/s12035-019-01859-4.
[PMID] 31903524.
2020
Large-scale proteomic analysis of Alzheimer’s disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation.
Nature medicine.
26(5):769-780
[DOI] 10.1038/s41591-020-0815-6.
[PMID] 32284590.
2020
Meta-Analysis of the Alzheimer’s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.
Cell reports.
32(2)
[DOI] 10.1016/j.celrep.2020.107908.
[PMID] 32668255.
2020
Metformin inhibits RAN translation through PKR pathway and mitigates disease in C9orf72 ALS/FTD mice.
Proceedings of the National Academy of Sciences of the United States of America.
117(31):18591-18599
[DOI] 10.1073/pnas.2005748117.
[PMID] 32690681.
2020
Scientific Advising and Reviewing: On strengthening the bond between the Alzheimer’s Association and the scientific community.
Alzheimer's & dementia : the journal of the Alzheimer's Association.
16(7):1095-1098
[DOI] 10.1002/alz.12059.
[PMID] 32426924.
2020
Utilizing minimally purified secreted rAAV for rapid and cost-effective manipulation of gene expression in the CNS.
Molecular neurodegeneration.
15(1)
[DOI] 10.1186/s13024-020-00361-z.
[PMID] 32122372.
2020
γ-Secretase modulators exhibit selectivity for modulation of APP cleavage but inverse γ-secretase modulators do not.
Alzheimer's research & therapy.
12(1)
[DOI] 10.1186/s13195-020-00622-5.
[PMID] 32430033.
2019
A cognitive stress test for prodromal Alzheimer’s disease: Multiethnic generalizability.
Alzheimer's & dementia (Amsterdam, Netherlands).
11:550-559
[DOI] 10.1016/j.dadm.2019.05.003.
[PMID] 31417955.
2019
ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons.
iScience.
19:448-449
[DOI] 10.1016/j.isci.2019.08.004.
[PMID] 31425915.
2019
Alzheimer’s disease phospholipase C-gamma-2 (PLCG2) protective variant is a functional hypermorph.
Alzheimer's research & therapy.
11(1)
[DOI] 10.1186/s13195-019-0469-0.
[PMID] 30711010.
2019
An anti-CRF antibody suppresses the HPA axis and reverses stress-induced phenotypes.
The Journal of experimental medicine.
216(11):2479-2491
[DOI] 10.1084/jem.20190430.
[PMID] 31467037.
2019
APP-Mediated Signaling Prevents Memory Decline in Alzheimer’s Disease Mouse Model.
Cell reports.
27(5):1345-1355.e6
[DOI] 10.1016/j.celrep.2019.03.087.
[PMID] 31042463.
2019
Cardiac MLC2 kinase is localized to the Z-disc and interacts with α-actinin2.
Scientific reports.
9(1)
[DOI] 10.1038/s41598-019-48884-w.
[PMID] 31467300.
2019
Combining P301L and S320F tau variants produces a novel accelerated model of tauopathy.
Human molecular genetics.
28(19):3255-3269
[DOI] 10.1093/hmg/ddz151.
[PMID] 31261380.
2019
Effect of age, ethnicity, sex, cognitive status and APOE genotype on amyloid load and the threshold for amyloid positivity.
NeuroImage. Clinical.
22
[DOI] 10.1016/j.nicl.2019.101800.
[PMID] 30991618.
2019
Free-water imaging of the hippocampus is a sensitive marker of Alzheimer’s disease.
NeuroImage. Clinical.
24
[DOI] 10.1016/j.nicl.2019.101985.
[PMID] 31470214.
2019
Harnessing Immunoproteostasis to Treat Neurodegenerative Disorders.
Neuron.
101(6):1003-1015
[DOI] 10.1016/j.neuron.2019.02.027.
[PMID] 30897353.
2019
Individual and combined presenilin 1 and 2 knockouts reveal that both have highly overlapping functions in HEK293T cells
Journal of Biological Chemistry.
294(29):11276-11285
[DOI] 10.1074/jbc.ra119.008041.
View on:
Publisher’s Site
2019
Individual and combined presenilin 1 and 2 knockouts reveal that both have highly overlapping functions in HEK293T cells.
The Journal of biological chemistry.
294(29):11276-11285
[DOI] 10.1074/jbc.RA119.008041.
[PMID] 31167792.
2019
Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in a tauopathy mouse model reduces C1q and normalizes clinical phenotype while increasing spread and state of phosphorylation of tau.
Molecular psychiatry.
24(9):1383-1397
[DOI] 10.1038/s41380-018-0258-3.
[PMID] 30283031.
2019
Intra- and extracellular β-amyloid overexpression via adeno-associated virus-mediated gene transfer impairs memory and synaptic plasticity in the hippocampus.
Scientific reports.
9(1)
[DOI] 10.1038/s41598-019-52324-0.
[PMID] 31685865.
2019
MAPT mutations, tauopathy, and mechanisms of neurodegeneration.
Laboratory investigation; a journal of technical methods and pathology.
99(7):912-928
[DOI] 10.1038/s41374-019-0197-x.
[PMID] 30742061.
2019
Neurite orientation dispersion and density imaging reveals white matter and hippocampal microstructure changes produced by Interleukin-6 in the TgCRND8 mouse model of amyloidosis.
NeuroImage.
202
[DOI] 10.1016/j.neuroimage.2019.116138.
[PMID] 31472250.
2019
Organotypic brain slice cultures to model neurodegenerative proteinopathies.
Molecular Neurodegeneration.
14(1)
[DOI] 10.1186/s13024-019-0346-0.
[PMID] 31791377.
2019
Phosphorylation of serine 305 in tau inhibits aggregation.
Neuroscience letters.
692:187-192
[DOI] 10.1016/j.neulet.2018.11.011.
[PMID] 30423399.
2019
rAAV-based brain slice culture models of Alzheimer’s and Parkinson’s disease inclusion pathologies.
The Journal of experimental medicine.
216(3):539-555
[DOI] 10.1084/jem.20182184.
[PMID] 30770411.
2018
Alzheimer’s disease: The right drug, the right time.
Science (New York, N.Y.).
362(6420):1250-1251
[DOI] 10.1126/science.aau0437.
[PMID] 30545877.
2018
Animal models of neurodegenerative diseases.
Nature neuroscience.
21(10):1370-1379
[DOI] 10.1038/s41593-018-0236-8.
[PMID] 30250265.
2018
Challenges in Passive Immunization Strategies to Treat Parkinson Disease.
JAMA neurology.
75(10):1180-1181
[DOI] 10.1001/jamaneurol.2018.0346.
[PMID] 29913004.
2018
Conserved brain myelination networks are altered in Alzheimer’s and other neurodegenerative diseases.
Alzheimer's & dementia : the journal of the Alzheimer's Association.
14(3):352-366
[DOI] 10.1016/j.jalz.2017.09.012.
[PMID] 29107053.
2018
Designing antibodies against LRRK2-targeted tau epitopes.
PloS one.
13(9)
[DOI] 10.1371/journal.pone.0204367.
[PMID] 30261006.
2018
Distinct differences in prion-like seeding and aggregation between Tau protein variants provide mechanistic insights into tauopathies.
The Journal of biological chemistry.
293(12)
[DOI] 10.1074/jbc.AAC118.002657.
[PMID] 29572329.
2018
Divergent brain gene expression patterns associate with distinct cell-specific tau neuropathology traits in progressive supranuclear palsy.
Acta neuropathologica.
136(5):709-727
[DOI] 10.1007/s00401-018-1900-5.
[PMID] 30136084.
2018
Genome-wide pleiotropy analysis of neuropathological traits related to Alzheimer’s disease.
Alzheimer's research & therapy.
10(1)
[DOI] 10.1186/s13195-018-0349-z.
[PMID] 29458411.
2018
High-affinity interactions and signal transduction between Aβ oligomers and TREM2.
EMBO molecular medicine.
10(11)
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Hippocampal expression of murine TNFα results in attenuation of amyloid deposition in vivo.
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Robust amyloid clearance in a mouse model of Alzheimer’s disease provides novel insights into the mechanism of amyloid-beta immunotherapy.
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IFN-gamma promotes complement expression and attenuates amyloid plaque deposition in amyloid beta precursor protein transgenic mice.
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Massive gliosis induced by interleukin-6 suppresses Abeta deposition in vivo: evidence against inflammation as a driving force for amyloid deposition.
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BRI2 (ITM2b) inhibits Abeta deposition in vivo.
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Off the beaten pathway: the complex cross talk between Notch and NF-kappaB.
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Transthyretin protects Alzheimer’s mice from the behavioral and biochemical effects of Abeta toxicity.
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Efficient neuronal gene transfer with AAV8 leads to neurotoxic levels of tau or green fluorescent proteins.
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Filling the gaps in the abeta cascade hypothesis of Alzheimer’s disease.
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Insights into the mechanisms of action of anti-Abeta antibodies in Alzheimer’s disease mouse models.
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Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi’s sarcoma tumor cells.
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Amyloid-beta immunization effectively reduces amyloid deposition in FcRgamma-/- knock-out mice.
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PubMed
2001
Presenilins as therapeutic targets for the treatment of Alzheimer’s disease.
Trends in molecular medicine.
7(6):264-9
[PMID] 11378516.
View on:
PubMed
2001
Reduced effectiveness of Abeta1-42 immunization in APP transgenic mice with significant amyloid deposition.
Neurobiology of aging.
22(5):721-7
[PMID] 11705631.
View on:
PubMed
2001
Reduction of Abeta accumulation in the Tg2576 animal model of Alzheimer’s disease after oral administration of the phosphatidyl-inositol kinase inhibitor wortmannin.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology.
15(1):16-18
[PMID] 11099491.
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PubMed
2000
An empirical model of gamma-secretase activity.
Annals of the New York Academy of Sciences.
920:233-40
[PMID] 11193156.
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PubMed
2000
Biochemical detection of Abeta isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer’s disease.
Biochimica et biophysica acta.
1502(1):172-87
[PMID] 10899442.
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PubMed
2000
Cell-free assays for gamma-secretase activity.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology.
14(15):2383-6
[PMID] 11024004.
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PubMed
2000
Presenilin 1 regulates pharmacologically distinct gamma -secretase activities. Implications for the role of presenilin in gamma -secretase cleavage.
The Journal of biological chemistry.
275(34):26277-84
[PMID] 10816583.
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PubMed
2000
The presenilin 1 C92S mutation increases abeta 42 production.
Biochemical and biophysical research communications.
277(1):261-3
[PMID] 11027672.
View on:
PubMed
2000
Variant Alzheimer’s disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations.
Annals of neurology.
48(5):806-8
[PMID] 11079548.
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PubMed
1999
A novel, non-nested reverse-transcriptase polymerase chain reaction (RT-PCR) test for the detection of the t(15;17) translocation: a comparative study of RT-PCR cytogenetics, and fluorescence In situ hybridization.
Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology.
4(3):195-209
[PMID] 10553020.
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PubMed
1999
gamma-Secretase, evidence for multiple proteolytic activities and influence of membrane positioning of substrate on generation of amyloid beta peptides of varying length.
The Journal of biological chemistry.
274(17):11914-23
[PMID] 10207012.
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PubMed
1996
Expression and analysis of presenilin 1 in a human neuronal system: localization in cell bodies and dendrites.
Proceedings of the National Academy of Sciences of the United States of America.
93(17):9223-8
[PMID] 8799182.
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PubMed
1994
Amyloid beta protein levels in cerebrospinal fluid are elevated in early-onset Alzheimer’s disease.
Annals of neurology.
36(6):903-11
[PMID] 7998778.
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PubMed
1994
An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants.
Science (New York, N.Y.).
264(5163):1336-40
[PMID] 8191290.
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PubMed
1993
Human neurons derived from a teratocarcinoma cell line express solely the 695-amino acid amyloid precursor protein and produce intracellular beta-amyloid or A4 peptides.
Proceedings of the National Academy of Sciences of the United States of America.
90(20):9513-7
[PMID] 8415732.
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PubMed
1993
Production of amyloid beta protein from normal amyloid beta-protein precursor (beta APP) and the mutated beta APPS linked to familial Alzheimer’s disease.
Annals of the New York Academy of Sciences.
695:103-8
[PMID] 8239266.
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PubMed
1993
Release of excess amyloid beta protein from a mutant amyloid beta protein precursor.
Science (New York, N.Y.).
259(5094):514-6
[PMID] 8424174.
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PubMed
1993
Serine protease inhibitor antithrombin III and its messenger RNA in the pathogenesis of Alzheimer’s disease.
The American journal of pathology.
143(3):886-93
[PMID] 8362984.
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PubMed
1992
Normal processing of the Alzheimer’s disease amyloid beta protein precursor generates potentially amyloidogenic carboxyl-terminal derivatives.
Annals of the New York Academy of Sciences.
674:138-48
[PMID] 1288359.
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PubMed
1992
Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor.
Science (New York, N.Y.).
255(5045):726-8
[PMID] 1738846.
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PubMed
1992
Production of the Alzheimer amyloid beta protein by normal proteolytic processing.
Science (New York, N.Y.).
258(5079):126-9
[PMID] 1439760.
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PubMed
1992
Secretory processing of the Alzheimer amyloid beta/A4 protein precursor is increased by protein phosphorylation.
Biochemical and biophysical research communications.
187(3):1285-90
[PMID] 1417805.
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PubMed
1991
Serum amyloid P in Alzheimer’s disease. Implications for dysfunction of the blood-brain barrier.
Annals of the New York Academy of Sciences.
640:145-8
[PMID] 1776732.
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PubMed
1990
Analysis of the beta-amyloid protein precursor of Alzheimer’s disease: mRNAs and protein products.
Advances in neurology.
51:181-4
[PMID] 2104687.
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PubMed
1990
Expression of beta amyloid protein precursor mRNAs: recognition of a novel alternatively spliced form and quantitation in Alzheimer’s disease using PCR.
Neuron.
4(2):253-67
[PMID] 2106330.
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PubMed
1989
The beta amyloid protein precursor: mRNAs, membrane-associated forms, and soluble derivatives.
Progress in clinical and biological research.
317:971-84
[PMID] 2513588.
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PubMed
1988
Amyloid protein precursor messenger RNAs: differential expression in Alzheimer’s disease
Science.
241:1080-1084
1988
Amyloid protein precursor messenger RNAs: differential expression in Alzheimer’s disease.
Science (New York, N.Y.).
241(4869):1080-4
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1988
Evolution of the IgA heavy chain gene in the genus Mus.
Genetics.
119(4):925-31
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PubMed
1988
In situ hybridization of nucleus basalis neurons shows increased beta-amyloid mRNA in Alzheimer disease.
Proceedings of the National Academy of Sciences of the United States of America.
85(4):1227-31
[PMID] 3277188.
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1986
Evolution of the mouse IgA gene: nucleotide sequence comparison of IgA in BALB/c and Mus pahari.
Current topics in microbiology and immunology.
127:141-8
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High affinity interactions and signal transduction between Aβ oligomers and TREM2
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Publisher’s Site
Grants
Sep 2020
ACTIVE
Identifying and understanding the role of repeat RNAs and RAN proteins in Alzheimer's disease
Role: Other
Funding: NATL INST OF HLTH NIA
Sep 2020
ACTIVE
A Systems Approach to Targeting Innate Immunity in AD
Role: Principal Investigator
Funding: MAYO CLINIC
via NATL INST OF HLTH NIA
Aug 2020
ACTIVE
Interdisciplinary Training in Movement Disorders and Neurorestoration
Role: Co-Investigator
Funding: NATL INST OF HLTH NINDS
Jun 2020
ACTIVE
1Florida Alzheimers Disease Research Center
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Sep 2019
ACTIVE
Modulation of Alzheimers disease by Herpes simplex virus infection
Role: Principal Investigator
Funding: UNIV OF WASHINGTON
via NATL INST OF HLTH NIA
Aug 2019
ACTIVE
Elucidating factors that modulate tauopathy and cellular degeneration to guide therapeutic development
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Aug 2019
ACTIVE
Immunotherapy targeting the HPA axis in Alzheimers disease
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Sep 2018
– Aug 2020
A Systems Approach to Targeting Innate Immunity in AD
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Jul 2018
– Feb 2021
Understanding and Targeting Tau-induced Neurodegeneration
Role: Other
Funding: BRIGHTFOCUS FOU
Jun 2018
ACTIVE
APOE as a modifier of prion-like spread in dementia
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Feb 2018
– Aug 2020
Periodontal Bacteria augment Progression of Abeta and Tau Pathology
Role: Co-Investigator
Funding: FL DEPT OF HLTH ED ETHEL MOORE ALZHEIMER
Feb 2018
ACTIVE
Towards Understanding the Biological Role of Newly Discovered Alzheimers Disease Susceptibility Genes Affecting Immune Function
Role: Co-Investigator
Funding: FL DEPT OF HLTH ED ETHEL MOORE ALZHEIMER
Sep 2017
ACTIVE
Immunotherapeutic Targeting of Corticotropin-Releasing Hormone in Alzheimers Disease
Role: Other
Funding: NATL INST OF HLTH NINDS
Sep 2017
– May 2018
APOE as a modifier of prion-like spread in dementia
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Aug 2017
– Jul 2020
Periodontal bacteria and Alzheimers disease
Role: Co-Investigator
Funding: NATL INST OF HLTH NINDS
Jan 2016
ACTIVE
Miscellaneous Donors (Dr. Golde)
Role: Principal Investigator
Funding: MISCELLANEOUS DONORS
Aug 2015
ACTIVE
University of Florida – Mt. Sinai Medical Center AD Research Center
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Aug 2015
– Dec 2016
Exploring the positive effects of rAAV-IL-10 in a ALS mouse model
Role: Principal Investigator
Funding: AMYOTROPHIC LATERAL SCLEROSIS ASSOC
Jul 2015
ACTIVE
NACC YR 17 DATA COORDINATING CENTER SUBAWARD
Role: Principal Investigator
Funding: UNIV OF WASHINGTON
via NATL INST OF HLTH
Jun 2015
– May 2017
rAAV based somatic sheep brain and spinal cord
Role: Principal Investigator
Funding: UF DSR OPPORTUNITY FUND
May 2014
– Feb 2019
Immune-Mediated Mechanisms underlying CNS Abeta Clearance
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Sep 2013
– Aug 2019
Targeting Multiple Diseases Through Gamma Secretase
Role: Principal Investigator
Funding: UNIV OF MASSACHUSETTS
via NATL INST OF HLTH NCI
Sep 2013
– Aug 2018
A Systems Approach to Targeting Innate Immunity in AD
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Jul 2010
ACTIVE
Therapeutic Discovery in Neurodegenerative Disease
Role: Principal Investigator
Funding: FL CLINICAL PRACTICE ASSO
Patents
Issued
July 2018
Compounds for Treating Neurodegenerative Proteinopathies
#10,030,067
Published
June 2018
Compounds For Treating Neurodegenerative Proteinopathies (DIV)
#US18/0355018
Published
April 2010
Reducing Abeta42 Levels and Abeta Aggregation (MAYO CLINIC)
#2011/0021471 A1
Education
Chief Resident Clinical Pathology and Laboratory Medicine
1995-1996
·
University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania
Resident Clinical Pathology and Laboratory Medicine
1994-1996
·
University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania
Postdoctoral Fellow, Neuroscience Training Grant
1991-1992
·
Case Western Reserve Universit ; Mentor: Steven G. Younkin M.D., Ph.D.
Research Associate
1990-1991
·
Institute of Pathology Case Western Reserve University; Mentor: Steven G. Younkin, M.D. Ph.D
MD PhD, NIH funded Medical Scientist Training Program (MSTP)
1985-1994
·
Case Western Reserve University
BA
1981-1985
·
Amherst College
Teaching Profile
Courses Taught
2020
GMS6252 Molecular Therapy II ? Disease Targets and Applications
2019
GMS6757 Introduction to Alzheimer’s Disease and Related Dementias: Clinical and Mechanistic Principles
2018
GMS7980 Research for Doctoral Dissertation
2017
EGN4912 Engineering Directed Independent Research
2010-2013,2015-2016
GMS6750 Molecular Pathobiology of Neural Disease
2013-2015
GMS7794 Neuroscience Seminar
2013-2014
PHA5902 Research Pharmacodyna
2013
GMS6029 Brain Journal Club
Contact Details
Phones:
- Business:
- (352) 273-9456
Emails:
- Business:
- tgolde@ufl.edu