Research Topics
Genomes and Genes | Michael HuttonSummaryAffiliation: Mayo Clinic Country: USA Publications
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Publications
Microtubule-associated protein tau as a therapeutic target in neurodegenerative diseaseHanno M Roder
Mayo Clinic, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Expert Opin Ther Targets 11:435-42. 2007..In this review, the authors discuss some of the main therapeutic ideas presently advanced in the field and their molecular rationales...
Progranulin in frontotemporal lobar degeneration and neuroinflammationZeshan Ahmed
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
J Neuroinflammation 4:7. 2007....- Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTDParastoo Momeni
Laboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, MD, USA
BMC Neurol 6:44. 2006..A new locus for amyotrophic lateral sclerosis--frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p... - The presenilins and Alzheimer's diseaseM Hutton
Neurogenetics Laboratory, The Mayo Clinic Jacksonville, FL 32224, USA
Hum Mol Genet 6:1639-46. 1997.... - Analysis of tauopathies with transgenic miceM Hutton
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, USA
Trends Mol Med 7:467-70. 2001..Recent progress in the development of transgenic mouse models of human tauopathy is allowing these questions to be addressed... - Molecular genetics of chromosome 17 tauopathiesM Hutton
Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Ann N Y Acad Sci 920:63-73. 2000.... - Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17M Hutton
Mayo Clinic Jacksonville, Florida 32224, USA
Nature 393:702-5. 1998..The increase in exon 10+ messenger RNA will increase the proportion of Tau containing four microtubule-binding repeats, which is consistent with the neuropathology described in several families with FTDP-17... - Progressive white matter pathology in the spinal cord of transgenic mice expressing mutant (P301L) human tauWen Lang Lin
Mayo Clinic College of Medicine, Jacksonville, Florida, 32224, USA
J Neurocytol 34:397-410. 2005..The progressive axonal pathology is most consistent with a dying-back process caused by abnormal accumulation of tau in upstream neurons, while vacuolar myelinopathy may be a secondary manifestation of neuroinflammation... - Phosphorylated p38MAPK specific antibodies cross-react with sarkosyl-insoluble hyperphosphorylated tau proteinsNaruhiko Sahara
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA
J Neurochem 90:829-38. 2004..Together, the results indicate that the cross-reactivity of antiactive-p38MAPK antibody with phosphorylated tau is responsible for the immunolabeling of tau-positive inclusion... - Ultrastructural neuronal pathology in transgenic mice expressing mutant (P301L) human tauWen-Lang Lin
Mayo Clinic, Jacksonville, Florida 32224, USA
J Neurocytol 32:1091-105. 2003..These P301L transgenic mice exhibit many features common to human tauopathies, making them a valuable model to study the pathogenesis of these uncommon disorders... 
The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteinsChad A Dickey
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
J Clin Invest 117:648-58. 2007....- Elevated amyloid beta protein (Abeta42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator geneNilufer Ertekin-Taner
Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Hum Mol Genet 14:447-60. 2005..PLAU_1 is a plausible pathogenic mutation that could act by increasing Abeta42, but additional biological experiments are required to show this definitively... - Co-localization of glycogen synthase kinase-3 with neurofibrillary tangles and granulovacuolar degeneration in transgenic miceTakashi Ishizawa
Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL 32225, USA
Am J Pathol 163:1057-67. 2003.... - Deletion of the ubiquitin ligase CHIP leads to the accumulation, but not the aggregation, of both endogenous phospho- and caspase-3-cleaved tau speciesChad A Dickey
Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA
J Neurosci 26:6985-96. 2006..Based on these findings, we propose that polyubiquitination of tau by CHIP may facilitate the formation of insoluble filamentous tau lesions... - Presenilin 1 mutation in an african american family presenting with atypical Alzheimer dementiaGregory A Rippon
Department of Neurology, Mayo Clinic, Rochester, MN, USA
Arch Neurol 60:884-8. 2003..The M139V mutation can lead to atypical AD, and genetic background may have a role in determining the phenotype of genetically defined AD... - A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathyAndrew Grover
Laboratory of Neurogenetics, Neuroscience Department, Mayo Clinic, Jacksonville, FL 32224, USA
Exp Neurol 184:131-40. 2003.... - The L266V tau mutation is associated with frontotemporal dementia and Pick-like 3R and 4R tauopathyMarion Hogg
Neurogenetics Laboratory, Mayo Clinic Jacksonville, Jacksonville, Florida, USA
Acta Neuropathol 106:323-36. 2003..In addition, the results of the RD3 and ET3 immunostains clearly explain for the first time the presence of both 3R and 4R tau isoforms in preparations of insoluble tau from some Pick's disease cases... - A decade of modeling Alzheimer's disease in transgenic miceEileen McGowan
Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Trends Genet 22:281-9. 2006..The relationship between these lesions, neurodegeneration and development of the clinical syndrome will be explored... - The genetics of frontotemporal dementiaKristoffer Haugarvoll
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Neurol Clin 25:697-715, vi. 2007..The clinical and neuropathologic features of frontotemporal dementia with parkinsonism linked to chromosome 17 and the nature of the mutations in the progranulin and microtubule-associated protein tau genes are emphasized... - Filling the gaps in the abeta cascade hypothesis of Alzheimer's diseaseTodd E Golde
Mayo Clinic College of Medicine, Department of Neuroscience, Mayo Clinic Jacksonville 4500 San Pablo Rd, Jacksonville, Florida 32224, USA
Curr Alzheimer Res 3:421-30. 2006.... - Clinical features and disease haplotypes of individuals with the N279K tau gene mutation: a comparison of the pallidopontonigral degeneration kindred and a French familyYoshio Tsuboi
Department of Neurology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224, USA
Arch Neurol 59:943-50. 2002..Results of genealogical and molecular genetic studies determined that the families were not related. The N279K mutations found in both families have independent origins... - Clearing tau pathology with Abeta immunotherapy--reversible and irreversible stages revealedMichael Hutton
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Neuron 43:293-4. 2004..This result supports a primary role for Abeta in AD etiology... 
Progranulin gene mutation with an unusual clinical and neuropathologic presentationChristian Wider
Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA
Mov Disord 23:1168-73. 2008..This study further expands the clinical and pathological spectrum of PGRN mutations, and suggests the diagnosis could be missed in some individuals with atypical presentations...- Filamentous tau in oligodendrocytes and astrocytes of transgenic mice expressing the human tau isoform with the P301L mutationWen-Lang Lin
Mayo Clinic, Jacksonville, Florida, USA
Am J Pathol 162:213-8. 2003..Given similarities of the lesions in the mice to human neuronal and glial inclusions, these transgenic mice appear to be a valuable model to study pathogenesis of the neurodegenerative tauopathies... - Fine mapping of the alpha-T catenin gene to a quantitative trait locus on chromosome 10 in late-onset Alzheimer's disease pedigreesNilufer Ertekin-Taner
Department of Neuroscience, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA
Hum Mol Genet 12:3133-43. 2003..These findings indicate that VR22 has variant(s) which influence Abeta42 and contribute to the previously reported linkage for plasma Abeta42 in LOAD families... - HSP induction mediates selective clearance of tau phosphorylated at proline-directed Ser/Thr sites but not KXGS (MARK) sitesChad A Dickey
Mayo Clinic Jacksonville, College of Medicine, Jacksonville, Florida, USA
FASEB J 20:753-5. 2006.... - Frontotemporal dementia and parkinsonism associated with the IVS1+1G->A mutation in progranulin: a clinicopathologic studyBradley F Boeve
Department of Neurology, Mayo Clinic Rochester, MN 55905, USA
Brain 129:3103-14. 2006..These findings suggest that the insR352 PSEN1 is not pathogenic, and the IVS1+1G-->A mutation in PGRN causes FTDP associated with FTLD-U pathology and represents a new class of neurodegenerative disease--the 'hypoprogranulinopathies'... - Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairmentRichard J Caselli
Department of Neurology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA
Arch Neurol 64:1306-11. 2007..These changes could represent presymptomatic disease in some, despite their youth... - Progressive supranuclear palsy: pathology and geneticsDennis W Dickson
Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
Brain Pathol 17:74-82. 2007..Imaging studies suggest that there may be sensitive and specific means to differentiate PSP from other parkinsonian disorders, but identification of a diagnostic biomarker is still elusive... - The effect of tau genotype on clinical features in FTDP-17Yasuhiko Baba
Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Parkinsonism Relat Disord 11:205-8. 2005..7; 95% confidence interval, 1.4-98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17... - Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementiaRosa Rademakers
Department of Neuroscience, Mayo Clinic, Jacksonville, FL FL 32224, USA
Hum Mol Genet 17:3631-42. 2008..Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders... - Increase in tau tyrosine phosphorylation correlates with the formation of tau aggregatesIrving E Vega
Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA
Brain Res Mol Brain Res 138:135-44. 2005..The results suggest that tyrosine phosphorylation is as important as phosphorylation of other residues in tauopathy... - Early onset familial Alzheimer Disease with spastic paraparesis, dysarthria, and seizures and N135S mutation in PSEN1Leslie A Rudzinski
Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA
Alzheimer Dis Assoc Disord 22:299-307. 2008.... - Atypical progressive supranuclear palsy with corticospinal tract degenerationKeith A Josephs
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
J Neuropathol Exp Neurol 65:396-405. 2006..The clinicopathologic features of these 12 cases expand the spectrum of 4R tauopathies... - Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindredYasuhiko Baba
Department of Neurology, Mayo Clinic College of Medicine, Jacksonville, FL, USA
Acta Neuropathol (Berl) 111:300-11. 2006..Immunohistochemistry for APP and alphaB-crystallin demonstrates distinctive neurodegeneration in cerebral axons and perikarya... - A presenilin 1 mutation associated with familial frontotemporal dementia inhibits gamma-secretase cleavage of APP and notchZareen Amtul
Department of Neuroscience and Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Neurobiol Dis 9:269-73. 2002..The distinct clinical phenotype associated with this mutation suggests that chronic partial inhibition of gamma-secretase activity may result in neurodegeneration... - Clinical-pathologic study of biomarkers in FTDP-17 (PPND family with N279K tau mutation)Zoe Arvanitakis
Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
Parkinsonism Relat Disord 13:230-9. 2007..Autopsy of six affected subjects showed frontotemporal degeneration with extensive tauopathy. Further studies of FTDP-17 patients are needed to replicate these findings... - Neuropathologic features of frontotemporal lobar degeneration with ubiquitin-positive inclusions with progranulin gene (PGRN) mutationsKeith A Josephs
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA
J Neuropathol Exp Neurol 66:142-51. 2007..On the other hand, there is no histopathologic feature or combination of features that is pathognomonic. Neuronal intranuclear inclusions are virtually always present, but they can be detected in PGRN(-) cases... - TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's diseaseCatalina Amador-Ortiz
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Ann Neurol 61:435-45. 2007.... - Voxel-based morphometry in frontotemporal lobar degeneration with ubiquitin-positive inclusions with and without progranulin mutationsJennifer L Whitwell
Division of Behavioral Neurology, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
Arch Neurol 64:371-6. 2007..Mutations in the progranulin gene (PGRN) have recently been identified as a cause of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) in some families... - Accelerated lipofuscinosis and ubiquitination in granulin knockout mice suggest a role for progranulin in successful agingZeshan Ahmed
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
Am J Pathol 177:311-24. 2010..Our data suggests that PGRN plays a key role in maintaining neuronal function during aging and supports the notion that PGRN is a trophic factor essential for long-term neuronal survival... - Heredofamilial brain calcinosis syndromeYasuhiko Baba
Department of Neurology, Mayo Clinic College of Medicine, Jacksonville, Fla 32224, USA
Mayo Clin Proc 80:641-51. 2005..We review conditions associated with heredofamilial BCS in which brain calcinosis is nearly uniformly present because such information may be Important to the clinician pursuing an investigative strategy... - Neurofibrillary tangle-related synaptic alterations of spinal motor neurons of P301L tau transgenic miceOmi Katsuse
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Neurosci Lett 409:95-9. 2006..In addition, synaptic boutons were detached from NFT-bearing neurons with the resulting space occupied by astrocytic processes, suggesting that astrocytes may be involved in the observed synaptic alterations... - Association between apolipoprotein E genotype and Alzheimer disease in African American subjectsNeill R Graff-Radford
Genetics Program L 320, Boston University School of Medicine, 715 Albany St, Boston, MA 02118, USA
Arch Neurol 59:594-600. 2002..The association between Alzheimer disease (AD) and genotypes at the apolipoprotein E (APOE) locus has been confirmed in numerous populations worldwide, but appears to be inconsistent in African American subjects... - High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsyRosa Rademakers
Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Belgium
Hum Mol Genet 14:3281-92. 2005..Thus, risk variants on different H1 htSNP haplotypes and protective variants on H2 contribute to population risk for PSP... - APOE epsilon 4 lowers age at onset and is a high risk factor for Alzheimer's disease; a case control study from central NorwaySigrid B Sando
Department of Neuroscience, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
BMC Neurol 8:9. 2008.... - GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriersEric M Reiman
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Neuron 54:713-20. 2007..Our findings suggest that GAB2 modifies LOAD risk in APOE epsilon4 carriers and influences Alzheimer's neuropathology... - Progranulin mutations in primary progressive aphasia: the PPA1 and PPA3 familiesMarsel Mesulam
Cognitive Neurology and Alzheimer s Disease Center and Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Ill 60611, USA
Arch Neurol 64:43-7. 2007..Primary progressive aphasia (PPA) is a language-based dementia characterized by fluent or nonfluent language disorder as its principal feature... - Identification of the genetic basis for complex disorders by use of pooling-based genomewide single-nucleotide-polymorphism association studiesJohn V Pearson
Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Am J Hum Genet 80:126-39. 2007.... - Haplotype-phenotype correlations in kindreds with the N279K mutation in the tau geneBryan K Woodruff
Arch Neurol 61:1327; author reply 1327. 2004
Research Grants
- Tau and Neurodegeneration II: A therapeutic targetMichael Hutton; Fiscal Year: 2007..Project 3 will study the impact of the chaperone Hsp70 and its co-chaperone CHIP on tau pathogenesis whilst Project 4, will examine the impact of tau phosphorylation on pathology and neurodegeneration...
- Amyloid and tau pathology in a transgenic modelMichael Hutton; Fiscal Year: 2006..abstract_text> ..
- Tangle Formation in P301L Transgenic MiceMichael Hutton; Fiscal Year: 2005....
- The genetics of chromosome 17q21-linked tau-negative FTDMichael Hutton; Fiscal Year: 2006..The identification of this gene will be a crucial step towards understanding the etiology of FTD as well as determining how this disease relates to MND. ..