Rudolph Tanzi

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Association of GSK3B with Alzheimer disease and frontotemporal dementia
    Barbara A J Schaffer
    Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 2506 Gonda, 695 Charles E Young Dr S, Los Angeles, CA 90095 1761, USA
    Arch Neurol 65:1368-74. 2008
  2. pmc The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide
    Stephanie J Soscia
    Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease and Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America
    PLoS ONE 5:e9505. 2010
  3. pmc RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing
    Zhongcong Xie
    Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 2060, USA
    Transl Neurodegener 1:8. 2012
  4. ncbi A brief history of Alzheimer's disease gene discovery
    Rudolph E Tanzi
    Genetics and Aging Research Unit, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    J Alzheimers Dis 33:S5-13. 2013
  5. pmc An AICD-based functional screen to identify APP metabolism regulators
    Can Zhang
    Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA, USA
    Mol Neurodegener 2:15. 2007
  6. ncbi New frontiers in Alzheimer's disease genetics
    R E Tanzi
    Genetics and Aging Research Unit, Center for Aging, Genetics, and Neurodegeneration, Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Neuron 32:181-4. 2001
  7. ncbi Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective
    Rudolph E Tanzi
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Massachussetts General Hospital, Harvard Medical School, Charlestown, Massachussetts 02129, USA
    Cell 120:545-55. 2005
  8. ncbi Clearance of Alzheimer's Abeta peptide: the many roads to perdition
    R E Tanzi
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown 02129, USA
    Neuron 43:605-8. 2004
  9. pmc Assessment of Alzheimer's disease case-control associations using family-based methods
    Brit Maren M Schjeide
    MassGeneral Institute for Neurodegenerative Disease MIND, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Neurogenetics 10:19-25. 2009
  10. ncbi Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1
    Yang Chang
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129 4404, USA
    J Biol Chem 278:51100-7. 2003

Research Grants

Detail Information

Publications85

  1. pmc Association of GSK3B with Alzheimer disease and frontotemporal dementia
    Barbara A J Schaffer
    Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 2506 Gonda, 695 Charles E Young Dr S, Los Angeles, CA 90095 1761, USA
    Arch Neurol 65:1368-74. 2008
    ..As a known tau kinase, GSK3B is a promising candidate gene in the remaining cases of FTD and in AD, for which tau mutations have not been found...
  2. pmc The Alzheimer's disease-associated amyloid beta-protein is an antimicrobial peptide
    Stephanie J Soscia
    Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease and Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America
    PLoS ONE 5:e9505. 2010
    ....
  3. pmc RNAi-mediated knock-down of Dab and Numb attenuate Aβ levels via γ-secretase mediated APP processing
    Zhongcong Xie
    Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 2060, USA
    Transl Neurodegener 1:8. 2012
    ..g. Notch, might be avoided...
  4. ncbi A brief history of Alzheimer's disease gene discovery
    Rudolph E Tanzi
    Genetics and Aging Research Unit, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
    J Alzheimers Dis 33:S5-13. 2013
    ..Here, I review the past, present, and future of attempts to elucidate the complex and heterogeneous genetic underpinnings of AD along with some of the unique events that made these discoveries possible...
  5. pmc An AICD-based functional screen to identify APP metabolism regulators
    Can Zhang
    Department of Bioscience and Biotechnology, Drexel University, Philadelphia, PA, USA
    Mol Neurodegener 2:15. 2007
    ..Production of AICD-Gal4 induces Gal4-UAS driven luciferase expression. Therefore, when regulators of APP metabolism are modulated, luciferase expression is altered...
  6. ncbi New frontiers in Alzheimer's disease genetics
    R E Tanzi
    Genetics and Aging Research Unit, Center for Aging, Genetics, and Neurodegeneration, Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Neuron 32:181-4. 2001
    ..In this review, we present a brief history of AD genetics and preview some of the next frontiers in Alzheimer gene discovery primarily focusing on chromosomes 12, 10, and 9...
  7. ncbi Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective
    Rudolph E Tanzi
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Massachussetts General Hospital, Harvard Medical School, Charlestown, Massachussetts 02129, USA
    Cell 120:545-55. 2005
    ..Here we assess the amyloid hypothesis based on both known and putative Alzheimer's disease genes...
  8. ncbi Clearance of Alzheimer's Abeta peptide: the many roads to perdition
    R E Tanzi
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown 02129, USA
    Neuron 43:605-8. 2004
    ..This minireview will summarize pathways involved in the removal of cerebral Abeta, including enzymatic degradation and receptor-mediated efflux out of the brain...
  9. pmc Assessment of Alzheimer's disease case-control associations using family-based methods
    Brit Maren M Schjeide
    MassGeneral Institute for Neurodegenerative Disease MIND, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Neurogenetics 10:19-25. 2009
    ..Further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes...
  10. ncbi Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1
    Yang Chang
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129 4404, USA
    J Biol Chem 278:51100-7. 2003
    ..Finally, although FE65L1 increases APP C-terminal domain production, it does not mediate the APP-dependent transcriptional activation observed with FE65...
  11. ncbi The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation
    Zhongcong Xie
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Charlestown, Massachusetts 02129 2060, USA
    J Neurosci 27:1247-54. 2007
    ..Accumulation of aggregated Abeta in the media can then promote apoptosis. The result is a vicious cycle of isoflurane-induced apoptosis, Abeta generation and aggregation, and additional rounds of apoptosis, leading to cell death...
  12. ncbi RNA interference-mediated silencing of X11alpha and X11beta attenuates amyloid beta-protein levels via differential effects on beta-amyloid precursor protein processing
    Zhongcong Xie
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129 4404, USA
    J Biol Chem 280:15413-21. 2005
    ..g. Notch, might be avoided...
  13. ncbi Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretion
    Mikko Hiltunen
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA
    J Biol Chem 281:32240-53. 2006
    ..These findings suggest that changes in UBQLN1 steady-state levels affect APP trafficking and processing, thereby influencing the generation of Abeta...
  14. ncbi RNA interference silencing of the adaptor molecules ShcC and Fe65 differentially affect amyloid precursor protein processing and Abeta generation
    Zhongcong Xie
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129 2060, USA
    J Biol Chem 282:4318-25. 2007
    ..These findings suggest that pharmacologically blocking interaction of APP with ShcC and Fe65 may provide novel therapeutic strategies against AD...
  15. ncbi Effects of RNA interference-mediated silencing of gamma-secretase complex components on cell sensitivity to caspase-3 activation
    Zhongcong Xie
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114 16th Street, Charlestown, MA 02129 2060, USA
    J Biol Chem 279:34130-7. 2004
    ..Collectively, these findings indicate that cellular sensitivity to caspase activation correlates with overall PS1 protein levels, particularly with levels of FL-PS1...
  16. ncbi Autoantibodies to redox-modified oligomeric Abeta are attenuated in the plasma of Alzheimer's disease patients
    Robert D Moir
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown 02129 4404, USA
    J Biol Chem 280:17458-63. 2005
    ..041) with plasma immunoreactivity to CAPS. These data suggest that autoantibodies to CAPS are depleted in AD patients and raise the prospect that immunization with anti-CAPS antibodies might provide therapeutic benefit for AD...
  17. ncbi BACE is degraded via the lysosomal pathway
    Young Ho Koh
    Genetics and Aging Research Unit, Massachusetts General Hospital, Charlestown, 02129, USA
    J Biol Chem 280:32499-504. 2005
    ..Collectively, our data indicate that BACE is transported to the late endosomal/lysosomal compartments where it is degraded via the lysosomal pathway and that the di-leucine motif plays a role in sorting BACE to lysosomes...
  18. pmc GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association results
    Brit Maren M Schjeide
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 114 16th St, Charlestown, MA 02129, USA
    Arch Neurol 66:250-4. 2009
    ..To our knowledge, these findings have not been independently replicated...
  19. ncbi Hypocapnia induces caspase-3 activation and increases Abeta production
    Zhongcong Xie
    Genetics and Aging Research Unit, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown 02129 4404, USA
    Neurodegener Dis 1:29-37. 2004
    ..Mutant forms of PS1 have been shown to sensitize cells to apoptotic cell death...
  20. pmc Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOE
    Lars Bertram
    Genetics and Aging Research Unit, Mass General Institute for Neurodegenerative Disease MIND, Department of Neurology, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Am J Hum Genet 83:623-32. 2008
    ....
  21. ncbi The current status of Alzheimer's disease genetics: what do we tell the patients?
    Lars Bertram
    Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
    Pharmacol Res 50:385-96. 2004
    ..This review focuses on the analytic tools used to identify genes in complex diseases, and then provides a summary of recent linkage and association findings indicating the existence of novel late-onset AD genes on several chromosomes...
  22. pmc Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein
    Wesley Farris
    Department of Neurology, Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Am J Pathol 164:1425-34. 2004
    ..Our findings have relevance for the emerging genetic evidence suggesting that IDE may be a late-onset AD-risk gene, and for the epidemiological relationships among hyperinsulinemia, DM2, and AD...
  23. ncbi An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript
    Jack T Rogers
    Genetics and Aging Research Unit, Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts 02129 4404, USA
    J Biol Chem 277:45518-28. 2002
    ....
  24. ncbi The LDLR locus in Alzheimer's disease: a family-based study and meta-analysis of case-control data
    Lars Bertram
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Neurobiol Aging 28:18.e1-4. 2007
    ..Based on our data, it seems unlikely that these genetic variants in LDLR make a significant contribution to AD risk in the general population...
  25. ncbi Alzheimer's disease drug discovery targeted to the APP mRNA 5'untranslated region
    Jack T Rogers
    Genetics and Aging Unit, Massachusetts General Hospital Harvard Medical School, Charlestown 02129 4404, USA
    J Mol Neurosci 19:77-82. 2002
    ..These APP 5'UTR directed drugs exemplify a new strategy to identify RNA-directed agents to lower APP translation and A beta peptide output for Alzheimer's disease therapeutics...
  26. ncbi The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels
    Zhongcong Xie
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129 4404, USA
    Anesthesiology 104:988-94. 2006
    ....
  27. ncbi Low-density lipoprotein receptor-related protein levels and endocytic function are reduced by overexpression of the FE65 adaptor protein, FE65L1
    SUZANNE Y GUENETTE
    Genetics and Aging Research Unit, Center for Aging Genetics and Neurodegeneration, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Neurochem 82:755-62. 2002
    ..These data show that FE65L1 can differentially affect the metabolic fate of APP and LRP. In addition, these data suggest that the LRP decrease observed in FE65L1 overexpressing cells may in part contribute to altered APP processing...
  28. ncbi Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high-throughput fluorescent plate reader
    Anne V Thomas
    Alzheimer s Disease Research Laboratory, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Biol Chem 281:26400-7. 2006
    ....
  29. doi Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses
    Lars Bertram
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Massachusetts General Hospital, 114 16th Street, Charlestown, Massachusetts 02129, USA
    Nat Rev Neurosci 9:768-78. 2008
    ..This Review discusses the putative pathogenetic roles and common biochemical pathways of some of the most genetically and biologically compelling of these potential AD risk factors...
  30. pmc Copper, beta-amyloid, and Alzheimer's disease: tapping a sensitive connection
    Ashley I Bush
    Genetics and Aging Research Unit, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 100:11193-4. 2003
  31. pmc The inhalation anesthetic desflurane induces caspase activation and increases amyloid beta-protein levels under hypoxic conditions
    Bin Zhang
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129 2060, USA
    J Biol Chem 283:11866-75. 2008
    ..Pending in vivo confirmation, these data may have profound implications for anesthesia care in elderly patients, and especially those with AD...
  32. ncbi Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
    Lars Bertram
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease MIND, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Nat Genet 39:17-23. 2007
    ..67 for protective alleles). Our database provides a powerful tool for deciphering the genetics of Alzheimer disease, and it serves as a potential model for tracking the most viable gene candidates in other genetically complex diseases...
  33. doi Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database
    Nicole C Allen
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Nat Genet 40:827-34. 2008
    ..As such, it could serve as a model for field synopses of genetic associations in other common and genetically complex disorders...
  34. ncbi HtrA2 regulates beta-amyloid precursor protein (APP) metabolism through endoplasmic reticulum-associated degradation
    Henri J Huttunen
    Neurobiology of Disease Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    J Biol Chem 282:28285-95. 2007
    ..Based on these results we suggest a novel function for HtrA2 as a regulator of APP metabolism through ER-associated degradation...
  35. ncbi Caspase activation increases beta-amyloid generation independently of caspase cleavage of the beta-amyloid precursor protein (APP)
    Giuseppina Tesco
    Genetics and Aging Research Unit, Center for Aging, Genetics and Neurodegeneration, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachussetts 02129, USA
    J Biol Chem 278:46074-80. 2003
    ..These findings indicate that the enhanced Abeta generation associated with apoptosis does not require cleavage of APP at its C-terminal (Asp720) and/or N-terminal caspase sites...
  36. pmc Reduced amyloidogenic processing of the amyloid beta-protein precursor by the small-molecule Differentiation Inducing Factor-1
    Michael A Myre
    Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Cell Signal 21:567-76. 2009
    ..Our findings suggest that DIF-1 affects G0/G1-associated amyloidogenic processing of APP by a gamma-secretase-, proteasome- and calpain-insensitive pathway, and that this effect requires the presence of residue Thr668...
  37. ncbi The role of the low-density lipoprotein receptor-related protein (LRP1) in Alzheimer's A beta generation: development of a cell-based model system
    Joy J Goto
    Genetics and Aging Research Unit, Center for Aging, Genetics and Neurodegeneration, Boston, MA 02129, USA
    J Mol Neurosci 19:37-41. 2002
    ..This cell-based model system and LRP-cluster II mini-receptor will be very useful for screening novel compounds that can reduce A beta accumulation by inhibiting binding of APP-KPI to LRP1...
  38. ncbi Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer's Abeta peptides
    Xudong Huang
    Department of Psychiatry, and Laboratory for Oxidation Biology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA
    J Biol Inorg Chem 9:954-60. 2004
    ..These data suggest that protein self-assembly and oligomerization are not spontaneous in this system as previously thought, and that there may be an obligatory role for metal ions in initiating Abeta amyloidosis and oligomerization...
  39. pmc The galvanization of beta-amyloid in Alzheimer's disease
    Ashley I Bush
    Genetics and Aging Research Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Proc Natl Acad Sci U S A 99:7317-9. 2002
  40. ncbi Redox-active metals, oxidative stress, and Alzheimer's disease pathology
    Xudong Huang
    Laboratory for Oxidation Biology, Genetics and Aging Research Unit, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Ann N Y Acad Sci 1012:153-63. 2004
    ....
  41. ncbi Family-based association between Alzheimer's disease and variants in UBQLN1
    Lars Bertram
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Charlestown 02129, USA
    N Engl J Med 352:884-94. 2005
    ..The gene encoding ubiquilin 1 (UBQLN1) is one of several candidate genes for Alzheimer's disease located near a well-established linkage peak on chromosome 9q22...
  42. pmc Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity
    Giuseppina Tesco
    Genetics and Aging Research Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
    Neuron 54:721-37. 2007
    ..In summary, we have elucidated a GGA3-dependent mechanism regulating BACE levels and beta-secretase activity. This mechanism may explain increased cerebral levels of BACE and Abeta following cerebral ischemia and existing in AD...
  43. pmc Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in mice
    Rebekah C Mannix
    Division of Emergency Medicine, Department of Medicine, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Cereb Blood Flow Metab 31:351-61. 2011
    ..The data suggest age-dependent effects of APOE4 on cognitive outcome after TBI, and that therapies targeting APOE4 may be more effective in adults versus children with TBI...
  44. pmc The genetic epidemiology of neurodegenerative disease
    Lars Bertram
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    J Clin Invest 115:1449-57. 2005
    ....
  45. ncbi Peroxidase activity of cyclooxygenase-2 (COX-2) cross-links beta-amyloid (Abeta) and generates Abeta-COX-2 hetero-oligomers that are increased in Alzheimer's disease
    Seiichi Nagano
    Laboratory for Oxidation Biology, Genetics and Aging Research Unit, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 279:14673-8. 2004
    ..COX-2-mediated cross-linking may inhibit Abeta catabolism and possibly generate toxic intracellular forms of oligomeric Abeta...
  46. pmc Familial Alzheimer's disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor generated by beta-secretase cleavage
    Can Zhang
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129 2060, USA
    Curr Alzheimer Res 7:21-6. 2010
    ..All four different PSEN1 FAD mutations tested (in three mammalian cell lines) did not alter sAPPbeta levels. Therefore PS1 mutations do not appear to contribute to AD pathogenesis via altered production of sAPPbeta...
  47. pmc Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity
    Minji Kim
    MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA
    Hum Mol Genet 18:3987-96. 2009
    ..5-3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD...
  48. pmc Therapeutics for Alzheimer's disease based on the metal hypothesis
    Ashley I Bush
    The Mental Health Research Institute, Parkville, Victoria, Australia
    Neurotherapeutics 5:421-32. 2008
    ..Small molecules targeting Abeta-metal interactions (e.g., PBT2) are currently advancing through clinical trials and show increasing promise as disease-modifying agents for Alzheimer's disease based on the "metal hypothesis."..
  49. ncbi Results of a high-resolution genome screen of 437 Alzheimer's disease families
    Deborah Blacker
    Massachusetts General Hospital, Charlestown, MA, USA
    Hum Mol Genet 12:23-32. 2003
    ..Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD...
  50. pmc Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein
    Can Zhang
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129 2060, USA
    J Biol Chem 285:28472-80. 2010
    ..These data provide a mechanism of action for the ability of curcumin to attenuate amyloid-beta pathology...
  51. ncbi Alzheimer's disease: the cholesterol connection
    Luigi Puglielli
    Neurobiology of Disease Laboratory, CAGN, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Nat Neurosci 6:345-51. 2003
    ..In this review, we describe recent findings concerning the molecular mechanisms underlying the cholesterol-AD connection...
  52. pmc Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo
    Wesley Farris
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:4162-7. 2003
    ....
  53. pmc Loss of function of ATXN1 increases amyloid beta-protein levels by potentiating beta-secretase processing of beta-amyloid precursor protein
    Can Zhang
    Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129 2060, USA
    J Biol Chem 285:8515-26. 2010
    ..Taken together, ATXN1 functions as a genetic risk modifier that contributes to AD pathogenesis through a loss-of-function mechanism by regulating beta-secretase cleavage of APP and Abeta levels...
  54. ncbi APP substitutions V715F and L720P alter PS1 conformation and differentially affect Abeta and AICD generation
    Giuseppina Tesco
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129 4404, USA
    J Neurochem 95:446-56. 2005
    ..In conclusion, both APPV715F and APPL720P change PS1 conformation with differential effects on Abeta and AICD production...
  55. ncbi Artefactual effects of lipid-based cell transfection reagents on AbetaPP processing and Abeta production
    Donna M Romano
    Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital and Harvard Medical School, MA 02129 2060, USA
    Amyloid 13:86-92. 2006
    ....
  56. ncbi Effects of RNAi-mediated silencing of PEN-2, APH-1a, and nicastrin on wild-type vs FAD mutant forms of presenilin 1
    Zhongcong Xie
    MassGeneral Institute for Neurodegenerative Disease, Department of NeurologyMassachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 2060, USA
    J Mol Neurosci 25:67-77. 2005
    ..In summary, the metabolism of wt-PS1 and FAD-linked Delta9-PS1 is specifically and differentially affected by loss of function of PEN-2...
  57. ncbi Alzheimer's disease and post-operative cognitive dysfunction
    Zhongcong Xie
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114 16th Street M3725, Charlestown, MA 02129 4404, USA
    Exp Gerontol 41:346-59. 2006
    ..More studies to assess the potential relationship between anesthesia/surgery and AD dementia are, therefore, urgently needed...
  58. pmc The common inhalational anesthetic sevoflurane induces apoptosis and increases beta-amyloid protein levels
    Yuanlin Dong
    Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Arch Neurol 66:620-31. 2009
    ..Subjects Naive mice, H4 human neuroglioma cells, and H4 human neuroglioma cells stably transfected to express full-length amyloid precursor protein...
  59. pmc Evidence of altered posteromedial cortical FMRI activity in subjects at risk for Alzheimer disease
    Maija Pihlajamaki
    Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, MA, USA
    Alzheimer Dis Assoc Disord 24:28-36. 2010
    ..Altered fMRI activity of the posteromedial areas of the brain default network may be an early indicator of risk for AD...
  60. ncbi LRP-mediated clearance of Abeta is inhibited by KPI-containing isoforms of APP
    Robert D Moir
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, and Neurology, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Curr Alzheimer Res 2:269-73. 2005
    ..Most significantly, our data suggests that the elevated levels of APP-KPI in AD brain may attenuate the clearance of Abeta, the proteins own amyloidogenic catabolic product...
  61. ncbi Isolation and characterization of the Drosophila ubiquilin ortholog dUbqln: in vivo interaction with early-onset Alzheimer disease genes
    Airong Li
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02128, USA
    Hum Mol Genet 16:2626-39. 2007
    ..Collectively, these data support in vivo functional interaction between UBQLN1 and the AD-associated genes, presenilin and APP, and provide further clues regarding the potential role of UBQLN1 in AD pathogenesis...
  62. pmc A genome-wide linkage and association scan reveals novel loci for autism
    Lauren A Weiss
    Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA
    Nature 461:802-8. 2009
    ..The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants...
  63. ncbi Genetic association of Alzheimer's disease with multiple polymorphisms in alpha-2-macroglobulin
    Aleister J Saunders
    Genetics and Aging Research Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
    Hum Mol Genet 12:2765-76. 2003
    ..However, the negative case - control studies suggest that any underlying pathogenic polymorphisms have a modest effect, and may operate primarily among individuals with a family history of AD...
  64. ncbi Tangles and neurodegenerative disease--a surprising twist
    Rudolph E Tanzi
    Genetics and Aging Research Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown, Mass, USA
    N Engl J Med 353:1853-5. 2005
  65. ncbi Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease
    Lee E Goldstein
    Laboratory for Oxidation Biology, Massachusetts General Hospital, Charlestown, MA 02129 4404, USA
    Lancet 361:1258-65. 2003
    ..We aimed to investigate the hypothesis that molecular pathological findings associated with Alzheimer's disease overlap in the lens and brain...
  66. ncbi Alzheimer's disease: one disorder, too many genes?
    Lars Bertram
    Genetics and Aging Research Unit, Department of Neurology and Mass General Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
    Hum Mol Genet 13:R135-41. 2004
    ..This should serve to greatly decrease the likelihood of false positive and false negative findings reported in future years...
  67. doi Effects of ubiquilin 1 on the unfolded protein response
    Alice Lu
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA, 02129 4404, USA
    J Mol Neurosci 38:19-30. 2009
    ..These findings suggest that overexpression UBQLN1 transcript variants TV1-3, but not TV4, exert a protective effect during the UPR by attenuating CHOP induction and potentially increasing cell viability...
  68. ncbi Decreased catalytic activity of the insulin-degrading enzyme in chromosome 10-linked Alzheimer disease families
    Minji Kim
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129, and Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington 40536, USA
    J Biol Chem 282:7825-32. 2007
    ....
  69. ncbi Isoflurane-induced apoptosis: a potential pathogenic link between delirium and dementia
    Zhongcong Xie
    Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 4404, USA
    J Gerontol A Biol Sci Med Sci 61:1300-6. 2006
    ....
  70. pmc Single-nucleotide polymorphism rs498055 on chromosome 10q24 is not associated with Alzheimer disease in two independent family samples
    Lars Bertram
    Am J Hum Genet 79:180-3; author reply 183-4. 2006
  71. ncbi Preliminary studies of a novel bifunctional metal chelator targeting Alzheimer's amyloidogenesis
    Alpaslan Dedeoglu
    Geriatric Research Education and Clinical Center, Bedford Veterans Administration Medical Center, Bedford, MA 01730, USA
    Exp Gerontol 39:1641-9. 2004
    ..Collectively, these preliminary findings carry implication for XH1 being a BBB-permeable lead compound for AD therapeutics targeting Alzheimer's amyloidogenesis, although further studies are needed...
  72. ncbi Metalloenzyme-like activity of Alzheimer's disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H(2)O(2)
    Carlos Opazo
    Centro de Regulación Celular y Patología, Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago 114 D, Chile
    J Biol Chem 277:40302-8. 2002
    ..Cu. Therefore, microregional catalytic H(2)O(2) production, combined with the exhaustion of reducing agents, may mediate the neurotoxicity of Abeta in Alzheimer's disease, and inhibitors of this novel activity may be of therapeutic value...
  73. ncbi Exploring candidate gene associations with neuropsychological performance
    Matthew B McQueen
    Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, Colorado 80309 0447, USA
    Am J Med Genet B Neuropsychiatr Genet 144:987-91. 2007
    ....
  74. ncbi The synaptic Abeta hypothesis of Alzheimer disease
    Rudolph E Tanzi
    Nat Neurosci 8:977-9. 2005
  75. ncbi Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's disease
    Marian L Hamshere
    Biostatistics and Bioinformatics Unit, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
    Hum Mol Genet 16:2703-12. 2007
    ..Where samples overlapped, the genotyping consistency was high, estimated to average at 97.3%. Our large-scale linkage analysis consolidates clear evidence for a susceptibility locus for LOAD on 10q21.2...
  76. pmc Insulin-degrading enzyme is genetically associated with Alzheimer's disease in the Finnish population
    Saila Vepsäläinen
    J Med Genet 44:606-8. 2007
    ..Single locus findings were corroborated by the results obtained from haplotype analyses. This suggests that genetic alterations in or near the IDE gene may increase the risk for developing AD...
  77. pmc Is alpha-T catenin (VR22) an Alzheimer's disease risk gene?
    Lars Bertram
    J Med Genet 44:e63. 2007
    ..In these papers, evidence for association is mostly observed in multiplex families with Alzheimer's disease, whereas case-control samples of sporadic Alzheimer's disease are predominantly negative...
  78. doi Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta
    Paul A Adlard
    Oxidation Biology Laboratory, The Mental Health Research Institute of Victoria, Parkville, Victoria 3052, Australia
    Neuron 59:43-55. 2008
    ..The speed of recovery of the animals underscores the acutely reversible nature of the cognitive deficits associated with transgenic models of AD...
  79. ncbi Follow-up mapping supports the evidence for linkage in the candidate region at 9q22 in the NIMH Alzheimer's disease Genetics Initiative cohort
    Rodney T Perry
    Department of Epidemiology and International Health, University of Alabama at Birmingham, Birmingham, Alabama 35294 0022, USA
    Am J Med Genet B Neuropsychiatr Genet 144:220-7. 2007
    ..In an effort to pinpoint this putative AD susceptibility gene, we have begun to analyze SNPs in other candidate genes in and around this narrowed region to test for additional associations to AD...
  80. ncbi Metal exposure and Alzheimer's pathogenesis
    Guijian Liu
    Environmental Science Division, School of Earth and Space Sciences, University of Science and Technology of China, Hefei, China
    J Struct Biol 155:45-51. 2006
    ..Nevertheless, the study of APP and Abeta metallobiology may identify potential targets for therapeutic intervention and/or provide diagnostic methods for AD...
  81. doi Alzheimer's disease: The latest suspect
    Rudolph E Tanzi
    Nature 454:706-8. 2008
  82. ncbi Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial
    Craig W Ritchie
    Departments of Pathology, The University of Melbourne, The Mental Health Research Institute of Victoria, Parkville, Victoria, Australia
    Arch Neurol 60:1685-91. 2003
    ..Alzheimer disease (AD) may be caused by the toxic accumulation of beta-amyloid (Abeta)...
  83. ncbi Mapping autism risk loci using genetic linkage and chromosomal rearrangements
    Peter Szatmari
    Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario L8N 3Z5, Canada
    Nat Genet 39:319-28. 2007
    ..Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs...
  84. pmc Novel therapeutics for Alzheimer's disease
    Rudolph E Tanzi
    Neurotherapeutics 5:377-80. 2008

Research Grants14

  1. Identification and Characterization of Novel AD Genes
    Rudolph Tanzi; Fiscal Year: 2007
    ..The study has been led by Dr Rudolph Tanzi at Mass General Hospital in collaboration with co-investigators at the U Alabama and Johns Hopkins U These ..
  2. Alzheimer's Disease Genes, Cellular Pathways and Therapies
    Rudolph Tanzi; Fiscal Year: 2005
    ..This symposium will focus on genetic risk factors, relevant cellular pathways and emerging therapies for AD and frontal temporal dementia. ..
  3. Role of the g-secretase/PS1 complex in APP processing
    Rudolph Tanzi; Fiscal Year: 2003
    ....
  4. MECHANISM OF PRESENILIN 1--ASSOCIATED CELL DEATH
    Rudolph Tanzi; Fiscal Year: 2001
    ....
  5. MECHANISM OF PRESENILIN 1--ASSOCIATED CELL DEATH
    Rudolph Tanzi; Fiscal Year: 2000
    ....
  6. MECHANISM OF PRESENILIN 1--ASSOCIATED CELL DEATH
    Rudolph Tanzi; Fiscal Year: 1999
    ....