Research Topics
Genomes and Genes | M C IrizarrySummaryAffiliation: GlaxoSmithKline Research and Development Country: USA Publications
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Publications
Predictors of placebo group decline in the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) in 24 week clinical trials of Alzheimer's diseaseMichael C Irizarry
WW Epidemiology, GlaxoSmithKline, Harlow, UK
J Alzheimers Dis 14:301-11. 2008..Overcoming lack of placebo decline in AD clinical trials will require scales more sensitive to cognitive decline in mild AD and strategies to reduce within-person variability in outcome measures...
Incidence of new-onset seizures in mild to moderate Alzheimer diseaseMichael C Irizarry
Worldwide Epidemiology, GlaxoSmithKline, 5 Moore Dr, Research Triangle Park, NC 27709, USA
Arch Neurol 69:368-72. 2012..To estimate the incidence rate and predictors of seizures in patients with mild to moderate Alzheimer disease (AD)...- Predictors of placebo response in pooled lamotrigine neuropathic pain clinical trialsMichael C Irizarry
WW Epidemiology, GlaxoSmithKline, Research Triangle Park, NC, USA
Clin J Pain 25:469-76. 2009..The 574 patients in the pooled lamotrigine treatment arms were used as a replication dataset... - Plasma F2A isoprostane levels in Alzheimer's and Parkinson's diseaseM C Irizarry
Massachusetts Alzheimer s Disease Research Center, Massachusetts General Hospital, Boston, MA, USA
Neurodegener Dis 4:403-5. 2007..F2-isoprostane is a marker of lipid peroxidation which is elevated in AD CSF. Plasma F2-isoprostane has been proposed as a diagnostic marker for AD and mild cognitive impairment (MCI)... 
Plasma urate and progression of mild cognitive impairmentMichael C Irizarry
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
Neurodegener Dis 6:23-8. 2009..Impaired antioxidant defenses are implicated in neurodegenerative disease. The plasma levels of urate, a water-soluble antioxidant, are reduced in Alzheimer's disease (AD)...- Risk of cancer in patients exposed to gabapentin in two electronic medical record systemsMichael C Irizarry
WW Epidemiology, GlaxoSmithKline, Research Triangle Park, NC, USA
Pharmacoepidemiol Drug Saf 21:214-25. 2012..We explored the association between gabapentin and cancer in a US medical care program and followed up nominally significant associations in a UK primary care database... - Plasma beta-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathyM E Gurol
Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
Neurology 66:23-9. 2006..If confirmed in longitudinal studies, these data would suggest circulating beta-amyloid peptide as a novel biomarker or risk factor for microvascular damage in these common diseases of the elderly... - Plaque-induced abnormalities in neurite geometry in transgenic models of Alzheimer disease: implications for neural system disruptionR Le
Department of Neurology, Massachusetts General Hospital, Charlestown, USA
J Neuropathol Exp Neurol 60:753-8. 2001.... - Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative diseaseM C Irizarry
The Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA
Neurology 65:1402-8. 2005..tHcy may potentiate neurotoxic and vasculopathic processes, including amyloid beta protein (Abeta) metabolism, implicated in neurodegenerative diseases... - Glutamate receptor dysregulation in the hippocampus of transgenic mice carrying mutated human amyloid precursor proteinJ H Cha
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
Neurobiol Dis 8:90-102. 2001..These data suggest that mutant APP overexpression or age-related amyloid deposition produce a subtle specific alteration in hippocampal glutamate receptors with aging... - Plasma Abeta, homocysteine, and cognition: the Vitamin Intervention for Stroke Prevention (VISP) trialA Viswanathan
Hemorrhagic Stroke Research Program, Massachusetts General Hospital Stroke Research Center, 175 Cambridge Street, Suite 300, Boston, MA 02114, USA
Neurology 72:268-72. 2009.... - Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brainM Ingelsson
Harvard Medical School, Massachusetts General Hospital, Boston
Neurology 62:925-31. 2004.... - beta-site APP cleaving enzyme mRNA expression in APP transgenic mice: anatomical overlap with transgene expression and static levels with agingM C Irizarry
Alzheimer Disease Research Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA
Am J Pathol 158:173-7. 2001..Thus, hAPP and endogenous BACE expression in similar anatomical localizations allow for processing of hAPP and Abeta formation in hAPP transgenic mice, but these are modified by additional age-related and anatomical factors... - Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's diseaseB Urbanc
Center for Polymer Studies and Department of Physics, Boston University, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 99:13990-5. 2002..These results, along with computer simulations, suggest that Abeta develops neurotoxic properties in vivo when it adopts a fibrillar beta-pleated sheet conformation... - Clinical and biochemical correlates of insoluble alpha-synuclein in dementia with Lewy bodiesJ Klucken
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
Acta Neuropathol 111:101-8. 2006..However, the Triton X-100 soluble fraction of alpha-synuclein did correlate strongly with the expression of several heat shock proteins (HSPs) in DLB but not control cases, suggesting a coordinated HSP response in DLB neocortex... - Alzheimer disease therapeuticsM C Irizarry
Alzheimer Disease Research Unit, Center for Aging Genetics and Neurodegeneration, Massachusetts General Hospital, Boston, USA
J Neuropathol Exp Neurol 60:923-8. 2001..Rational neuroprotective approaches have led to recent trials of estrogen, antioxidant and anti-inflammatory medications in AD, and to the development of anti-amyloid strategies for delaying progression or preventing development of AD... - An exploration of cognitive subgroups in Alzheimer's diseaseJulie E Davidson
Memory Clinic Neuropsychology Center, University Hospital Basel, Basel, Switzerland
J Int Neuropsychol Soc 16:233-43. 2010.... - Elevation of cystatin C in susceptible neurons in Alzheimer's diseaseA Deng
Memory Disorders Clinic and the Alzheimer's Research Unit, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA
Am J Pathol 159:1061-8. 2001..These neuropathological observations reinforce the association between cystatin C and AD, and support a model of cystatin C involvement in the process of neuronal death in AD... - Alpha-synuclein has an altered conformation and shows a tight intermolecular interaction with ubiquitin in Lewy bodiesN Sharma
Department of Neurology, Massachusetts General Hospital East, Charlestown 02129, USA
Acta Neuropathol 102:329-34. 2001..These observations provide support for the hypothesis that in Lewy bodies alpha-synuclein adopts an altered three-dimensional structure and undergoes N-terminal ubiquitination... - Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease modelD M Holtzman
Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
Ann Neurol 47:739-47. 2000..These data demonstrate that ApoE facilitates the formation of both neuritic and cerebrovascular plaques, which are pathological hallmarks of AD and cerebral amyloid angiopathy... - Shorter telomeres may mark early risk of dementia: preliminary analysis of 62 participants from the nurses' health studyFrancine Grodstein
Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, and Harvard Medical School, Boston, Massachusetts, USA
PLoS ONE 3:e1590. 2008..Since telomeres shorten with age and oxidative stress, both of which are important contributors to the onset of dementia, telomere length might be a valuable biomarker... - Plasma amyloid beta-protein and C-reactive protein in relation to the rate of progression of Alzheimer diseaseJoseph J Locascio
Massachusetts Alzheimer s Disease Research Center, Wang Ambulatory Care Center, Suite 720, Room 731 G, Massachusetts General Hospital, 15 Parkman St, Boston, MA 02114, USA
Arch Neurol 65:776-85. 2008.... - Prevalence and effects of lobar microhemorrhages in early-stage dementiaAlireza Atri
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
Neurodegener Dis 2:305-12. 2005..The prevalence and effects of LMH detectable by gradient echo MRI (GE-MRI) in early-stage dementia are unknown... - Age but not diagnosis is the main predictor of plasma amyloid beta-protein levelsHiroaki Fukumoto
Department of Neurology, Massachusetts General Hospital, Boston, MA 02129, USA
Arch Neurol 60:958-64. 2003..CONCLUSIONS: Plasma Abeta measures increase with age, but, in contrast to reports on familial AD, plasma Abeta measures were neither sensitive nor specific for the clinical diagnosis of mild cognitive impairment or sporadic AD... - Prospective study of plasma folate, vitamin B12, and cognitive function and declineJae Hee Kang
Department of Medicine, Channing Laboratory, Brigham and Women s Hospital, Boston, MA, USA
Epidemiology 17:650-7. 2006..The relation between B vitamins and cognitive decline is controversial. In this study, we explored the association of plasma folate and vitamin B12 with cognitive function measured approximately 10 years later... - Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer diseaseHao Li
GlaxoSmithKline, Research Triangle Park, North Carolina, USA
Arch Neurol 65:45-53. 2008..To identify single-nucleotide polymorphisms (SNPs) associated with risk and age at onset of Alzheimer disease (AD) in a genomewide association study of 469 438 SNPs... - Performance characteristics of plasma amyloid-beta 40 and 42 assaysOlivia I Okereke
Division of Aging, Department of Medicine, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02115, USA
J Alzheimers Dis 16:277-85. 2009..While these preliminary findings suggest that measuring plasma Abeta(40) and Abeta(42) may be feasible in varied research settings, additional work in this area is necessary... - Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brainsMartin Ingelsson
Harvard Medical School, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
Acta Neuropathol 114:471-9. 2007..In conclusion, we demonstrated increased but largely variable 4R tau/3R tau mRNA ratios in FTLD and PSP cases, suggesting heterogeneous pathophysiological processes within these disorders... - Expression of APP pathway mRNAs and proteins in Alzheimer's diseaseToshifumi Matsui
Alzheimer Disease Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, MA 02129, USA
Brain Res 1161:116-23. 2007..These results suggest that altered transcription of APP in AD is proportionately associated with Abeta peptide, may occur in the context of gliosis, and may contribute to Abeta deposition in sporadic AD... - Plasma Abeta levels do not reflect brain Abeta levelsStefanie H Freeman
C S Kubik Laboratory for Neuropathology, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA
J Neuropathol Exp Neurol 66:264-71. 2007..We conclude that plasma levels of Abeta40 and Abeta42 are not robust correlates of histologic or biochemically assessed amyloid burdens in brain, although the influence of the APOE genotype should be further explored... - Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphismsJung Lee
Harvard Medical School, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
Exp Neurol 194:91-6. 2005..The results suggest that the investigated BDNF polymorphisms are neither robust genetic risk factors nor determinants of BDNF protein levels in AD... - LRP and senile plaques in Alzheimer's disease: colocalization with apolipoprotein E and with activated astrocytesKatrin Arelin
Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital, 114 16th Street, Room 2009, Charlestown, MA 02129, USA
Brain Res Mol Brain Res 104:38-46. 2002..The upregulation of LRP would allow increased clearance of LRP ligands as well as clearance of Abeta/ApoE complexes... - Biomarkers of Alzheimer disease in plasmaMichael C Irizarry
Alzheimer Disease Research Unit, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
NeuroRx 1:226-34. 2004.... - Demonstration of BACE (beta-secretase) phosphorylation and its interaction with GGA1 in cells by fluorescence-lifetime imaging microscopyChristine A F von Arnim
Alzheimer Disease Research Laboratory, Massachusetts General Hospital, Harvard Medical School, 114 16th Street, Charlestown, MA 02129, USA
J Cell Sci 117:5437-45. 2004.... - Lack of association of the cholesterol 24-hydroxylase (CYP46) intron 2 polymorphism with Alzheimer's diseaseMartin Ingelsson
Harvard Medical School, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
Neurosci Lett 367:228-31. 2004..Despite growing evidence implicating cholesterol metabolism in AD risk and Abeta generation, our data does not support a robust genetic relationship between the CYP46 intron 2 polymorphism and AD risk or neuropathology... - Coordinated expression of caspase 8, 3 and 7 mRNA in temporal cortex of Alzheimer disease: relationship to formic acid extractable abeta42 levelsToshifumi Matsui
Alzheimer Research Unit, Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
J Neuropathol Exp Neurol 65:508-15. 2006..Thus, a principal caspase pathway from caspase-8 to caspase-3 and/or 7 may contribute to neuron loss in AD brain... - No alteration in tau exon 10 alternative splicing in tangle-bearing neurons of the Alzheimer's disease brainMartin Ingelsson
Harvard Medical School, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA
Acta Neuropathol 112:439-49. 2006..In conclusion, this study indicated region-specific and possibly cell-type-specific tau splicing but did not lend any support to overt changes in alternative splicing of tau exon 10 being an underlying factor in AD pathogenesis... - A turn of the sulfatide in Alzheimer's diseaseMichael C Irizarry
Ann Neurol 54:7-8. 2003 - Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic miceTeresa Gomez-Isla
Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Neurobiol Aging 24:245-58. 2003..Thus, high expression of mutant human alpha-synuclein resulted in a progressive motor and widespread CNS gliotic phenotype independent of dopaminergic dysfunction in the Tg5093 line... - Beta-secretase protein and activity are increased in the neocortex in Alzheimer diseaseHiroaki Fukumoto
Alzheimer Disease Research Unit, Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital East, Bldg 114, Room 2010, 114 16th Street, Charlestown, MA 02129, USA
Arch Neurol 59:1381-9. 2002.... - Brain isoprostanes: a marker of lipid peroxidation and oxidative stress in ADMichael C Irizarry
Neurology 61:436-7. 2003 - Plasma beta amyloid and the risk of Alzheimer disease and dementia in elderly men: a prospective, population-based cohort studyJohan Sundelöf
Uppsala University, Department of Public Health and Geriatrics, Uppsala Science Park, Dag Hammarskölds väg 14B, Uppsala, Sweden
Arch Neurol 65:256-63. 2008..Beta amyloid (Abeta) protein accumulates in the brains of individuals with Alzheimer disease (AD) and is detectable in cerebrospinal fluid and plasma... - The normal equilibrium between CSF and plasma amyloid beta levels is disrupted in Alzheimer's diseaseVilmantas Giedraitis
Department of Public Health Geriatrics, Uppsala University, Uppsala, Sweden
Neurosci Lett 427:127-31. 2007..Our findings suggest that the normal equilibrium between CSF and plasma Abeta may be disrupted with the initiation of amyloid deposition in the brain... - APOE epsilon 3/ epsilon 4 heterozygotes have an elevated proportion of apolipoprotein E4 in cerebrospinal fluid relative to plasma, independent of Alzheimer's disease diagnosisHiroaki Fukumoto
Alzheimer Disease Research Unit, Massachusetts General Hospital East, B114 2010, 114 16th St, Charlestown, MA 02129, USA
Exp Neurol 183:249-53. 2003..However, the greater proportion of apoE4 in the cerebrospinal fluid suggests differential production or metabolism of the protein in the central nervous system (CNS), with the apoE4 isoform dominating... - Relation of quantitative indexes of concurrent alpha-synuclein abnormalities to clinical outcome in autopsy-proven Alzheimer diseaseRoee Holtzer
Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
Arch Neurol 63:226-30. 2006..There was no relation between quantitative neuropathologic indexes of LB abnormalities and clinical outcome. CONCLUSION: The variability of clinical features in AD was not related to the presence or degree of LB abnormalities... - 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... - Genotyping of apolipoprotein E: comparative evaluation of different protocolsMartin Ingelsson
Harvard Medical School/Massachusetts General Hospital, Charlestown, Massachusetts, USA
Curr Protoc Hum Genet . 2003..The latter approaches also provide the flexibility to investigate other polymorphic disease markers...