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Genomes and GenesSpecies | Rudolph TanziSummaryAffiliation: Harvard University Country: USA Publications
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Publications
Association of GSK3B with Alzheimer disease and frontotemporal dementiaBarbara 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...
A brief history of Alzheimer's disease gene discoveryRudolph 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...
An AICD-based functional screen to identify APP metabolism regulatorsCan 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...- New frontiers in Alzheimer's disease geneticsR 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... - Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspectiveRudolph 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... - Clearance of Alzheimer's Abeta peptide: the many roads to perditionR 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... - Assessment of Alzheimer's disease case-control associations using family-based methodsBrit 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... - Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1Yang 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... - The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulationZhongcong 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... - RNA interference-mediated silencing of X11alpha and X11beta attenuates amyloid beta-protein levels via differential effects on beta-amyloid precursor protein processingZhongcong 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... - Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretionMikko 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... - RNA interference silencing of the adaptor molecules ShcC and Fe65 differentially affect amyloid precursor protein processing and Abeta generationZhongcong 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... - Effects of RNA interference-mediated silencing of gamma-secretase complex components on cell sensitivity to caspase-3 activationZhongcong 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... - Autoantibodies to redox-modified oligomeric Abeta are attenuated in the plasma of Alzheimer's disease patientsRobert 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... - BACE is degraded via the lysosomal pathwayYoung 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... - GAB2 as an Alzheimer disease susceptibility gene: follow-up of genomewide association resultsBrit 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... - Genome-wide association analysis reveals putative Alzheimer's disease susceptibility loci in addition to APOELars 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.... - Hypocapnia induces caspase-3 activation and increases Abeta productionZhongcong 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..Hypocapnia (5 and 20 mm Hg CO2 for 6 h) also led to an increased Abeta production. CONCLUSION: The findings suggest that hypocapnia (e.g. during general anesthesia) could exacerbate AD neuropathogenesis... - 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... - Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-proteinWesley 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... - An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcriptJack 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.... - Redox-active metals, oxidative stress, and Alzheimer's disease pathologyXudong 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.... - HtrA2 regulates beta-amyloid precursor protein (APP) metabolism through endoplasmic reticulum-associated degradationHenri 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... - The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levelsZhongcong 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.... - 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... - Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high-throughput fluorescent plate readerAnne V Thomas
Alzheimer s Disease Research Laboratory, Harvard Medical School, Charlestown, Massachusetts 02129, USA
J Biol Chem 281:26400-7. 2006.... 
Reduced amyloidogenic processing of the amyloid beta-protein precursor by the small-molecule Differentiation Inducing Factor-1Michael 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...- Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene databaseLars 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... - Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analysesLars 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... - Therapeutics for Alzheimer's disease based on the metal hypothesisAshley 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.".. - Low-density lipoprotein receptor-related protein levels and endocytic function are reduced by overexpression of the FE65 adaptor protein, FE65L1SUZANNE 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... - Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene databaseNicole 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... - The role of the low-density lipoprotein receptor-related protein (LRP1) in Alzheimer's A beta generation: development of a cell-based model systemJoy 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... - Depletion of GGA3 stabilizes BACE and enhances beta-secretase activityGiuseppina 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... - Alzheimer's disease drug discovery targeted to the APP mRNA 5'untranslated regionJack 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... - The galvanization of beta-amyloid in Alzheimer's diseaseAshley 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 - The LDLR locus in Alzheimer's disease: a family-based study and meta-analysis of case-control dataLars 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... - Family-based association between Alzheimer's disease and variants in UBQLN1Lars 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... - Copper, beta-amyloid, and Alzheimer's disease: tapping a sensitive connectionAshley 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 - The genetic epidemiology of neurodegenerative diseaseLars 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.... - The inhalation anesthetic desflurane induces caspase activation and increases amyloid beta-protein levels under hypoxic conditionsBin 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... - 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 diseaseSeiichi 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... - Age-dependent effect of apolipoprotein E4 on functional outcome after controlled cortical impact in miceRebekah 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... - Familial Alzheimer's disease mutations in presenilin 1 do not alter levels of the secreted amyloid-beta protein precursor generated by beta-secretase cleavageCan 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... - Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer's Abeta peptidesXudong 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... - Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activityMinji 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... - Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor proteinCan 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... - Alzheimer's disease and post-operative cognitive dysfunctionZhongcong 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... - Effects of RNAi-mediated silencing of PEN-2, APH-1a, and nicastrin on wild-type vs FAD mutant forms of presenilin 1Zhongcong 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... - Results of a high-resolution genome screen of 437 Alzheimer's disease familiesDeborah 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... - Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivoWesley 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.... - Artefactual effects of lipid-based cell transfection reagents on AbetaPP processing and Abeta productionDonna 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.... - Alzheimer's disease: the cholesterol connectionLuigi 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... - Loss of function of ATXN1 increases amyloid beta-protein levels by potentiating beta-secretase processing of beta-amyloid precursor proteinCan 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... - APP substitutions V715F and L720P alter PS1 conformation and differentially affect Abeta and AICD generationGiuseppina 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... - The common inhalational anesthetic sevoflurane induces apoptosis and increases beta-amyloid protein levelsYuanlin 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... - Evidence of altered posteromedial cortical FMRI activity in subjects at risk for Alzheimer diseaseMaija 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... - LRP-mediated clearance of Abeta is inhibited by KPI-containing isoforms of APPRobert 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... - Isolation and characterization of the Drosophila ubiquilin ortholog dUbqln: in vivo interaction with early-onset Alzheimer disease genesAirong 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... - Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's diseaseLee E Goldstein
Laboratory for Oxidation Biology, Massachusetts General Hospital, Charlestown, MA 02129-4404, USA
Lancet 361:1258-65. 2003..INTERPRETATION: Abeta is present in the cytosol of lens fibre cells of people with Alzheimer's disease. Lens Abeta might promote regionally-specific lens protein aggregation, extracerebral amyloid formation, and supranuclear cataracts... - 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... - Genetic association of Alzheimer's disease with multiple polymorphisms in alpha-2-macroglobulinAleister 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... - Tangles and neurodegenerative disease--a surprising twistRudolph 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 - Decreased catalytic activity of the insulin-degrading enzyme in chromosome 10-linked Alzheimer disease familiesMinji 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.... - Effects of ubiquilin 1 on the unfolded protein responseAlice 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... - Isoflurane-induced apoptosis: a potential pathogenic link between delirium and dementiaZhongcong 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..These findings suggest that isoflurane-induced Abeta oligomerization and apoptosis may contribute to the risk of postoperative cognitive dysfunction and provide a potential pathogenic link between delirium and dementia... - Alzheimer's disease: The latest suspectRudolph E Tanzi
Nature 454:706-8. 2008 - Exploring candidate gene associations with neuropsychological performanceMatthew 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.... - Preliminary studies of a novel bifunctional metal chelator targeting Alzheimer's amyloidogenesisAlpaslan 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... - Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's diseaseMarian 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... - Insulin-degrading enzyme is genetically associated with Alzheimer's disease in the Finnish populationSaila 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... - The synaptic Abeta hypothesis of Alzheimer diseaseRudolph E Tanzi
Nat Neurosci 8:977-9. 2005 - Mapping autism risk loci using genetic linkage and chromosomal rearrangementsPeter 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... - Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trialCraig 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..CONCLUSION: Subject to the usual caveats inherent in studies with small sample size, this pilot phase 2 study supports further investigation of this novel treatment strategy using a metal-protein-attenuating compound... - Metal exposure and Alzheimer's pathogenesisGuijian 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... - Follow-up mapping supports the evidence for linkage in the candidate region at 9q22 in the NIMH Alzheimer's disease Genetics Initiative cohortRodney 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... - Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial AbetaPaul 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... - 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
, Departamento de Biologia Celular y Molecular, , , 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... - 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... - Single-nucleotide polymorphism rs498055 on chromosome 10q24 is not associated with Alzheimer disease in two independent family samplesLars Bertram
Am J Hum Genet 79:180-3; author reply 183-4. 2006 - Novel therapeutics for Alzheimer's diseaseRudolph E Tanzi
Neurotherapeutics 5:377-80. 2008
Research Grants
- Identification and Characterization of Novel AD GenesRudolph 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 ..
- Alzheimer's Disease Genes, Cellular Pathways and TherapiesRudolph Tanzi; Fiscal Year: 2005..This symposium will focus on genetic risk factors, relevant cellular pathways and emerging therapies for AD and frontal temporal dementia. ..
- Role of the g-secretase/PS1 complex in APP processingRudolph Tanzi; Fiscal Year: 2003....
- MECHANISM OF PRESENILIN 1--ASSOCIATED CELL DEATHRudolph Tanzi; Fiscal Year: 2001....