Rosa Rademakers

Summary

Affiliation: Mayo Clinic
Country: USA

Publications

  1. pmc Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida, USA
    Nat Genet 44:200-5. 2012
  2. pmc Progranulin axis and recent developments in frontotemporal lobar degeneration
    Alexandra M Nicholson
    Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Alzheimers Res Ther 4:4. 2012
  3. pmc Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis
    Nicola J Rutherford
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America
    PLoS Genet 4:e1000193. 2008
  4. doi request reprint Motor neuron disease in 2012: Novel causal genes and disease modifiers
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Nat Rev Neurol 9:63-4. 2013
  5. pmc Polymorphic genes of detoxification and mitochondrial enzymes and risk for progressive supranuclear palsy: a case control study
    Lisa F Potts
    Department of Anatomical Sciences and Neurobiology, University of Louisville, KY, USA
    BMC Med Genet 13:16. 2012
  6. ncbi request reprint The genetics of frontotemporal lobar degeneration
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Curr Neurol Neurosci Rep 7:434-42. 2007
  7. ncbi request reprint Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C-->T (Arg493X) mutation: an international initiative
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Lancet Neurol 6:857-68. 2007
  8. pmc Recent insights into the molecular genetics of dementia
    Rosa Rademakers
    Mayo Clinic, Department of Neuroscience, Jacksonville, FL 32224, USA
    Trends Neurosci 32:451-61. 2009
  9. pmc Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL FL 32224, USA
    Hum Mol Genet 17:3631-42. 2008
  10. pmc TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers
    N Finch
    Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Neurology 76:467-74. 2011

Detail Information

Publications102 found, 100 shown here

  1. pmc Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida, USA
    Nat Genet 44:200-5. 2012
    ..As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis...
  2. pmc Progranulin axis and recent developments in frontotemporal lobar degeneration
    Alexandra M Nicholson
    Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Alzheimers Res Ther 4:4. 2012
    ..The present review aims to underscore the necessity of further elucidation of PGRN biology in FTLD-related neurodegeneration...
  3. pmc Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis
    Nicola J Rutherford
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America
    PLoS Genet 4:e1000193. 2008
    ....
  4. doi request reprint Motor neuron disease in 2012: Novel causal genes and disease modifiers
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Nat Rev Neurol 9:63-4. 2013
    ..Novel ALS-linked genes and genetic modifiers were identified through screening in animal models and patients...
  5. pmc Polymorphic genes of detoxification and mitochondrial enzymes and risk for progressive supranuclear palsy: a case control study
    Lisa F Potts
    Department of Anatomical Sciences and Neurobiology, University of Louisville, KY, USA
    BMC Med Genet 13:16. 2012
    ....
  6. ncbi request reprint The genetics of frontotemporal lobar degeneration
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Curr Neurol Neurosci Rep 7:434-42. 2007
    ..In this report, we outline the progress made in the study of the genetic etiologies and neuropathologic substrates in FTLD...
  7. ncbi request reprint Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C-->T (Arg493X) mutation: an international initiative
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Lancet Neurol 6:857-68. 2007
    ..The most common mutation in GRN is Arg493X. We aimed to establish the contribution of this mutation to FTLD and related disorders...
  8. pmc Recent insights into the molecular genetics of dementia
    Rosa Rademakers
    Mayo Clinic, Department of Neuroscience, Jacksonville, FL 32224, USA
    Trends Neurosci 32:451-61. 2009
    ..These exciting findings provide novel insights into the disease mechanisms underlying dementia and hold promise for the development of potential treatments...
  9. pmc Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia
    Rosa 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...
  10. pmc TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers
    N Finch
    Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Neurology 76:467-74. 2011
    ....
  11. pmc C9ORF72 repeat expansions in cases with previously identified pathogenic mutations
    Marka van Blitterswijk
    From the Departments of Neuroscience M v B, M C B, M D H, M E M, N J R, P E B, T R, B M, P E A A, K F B, L P, D W D, R R and Neurology Z K W, K B B, N R G R, Mayo Clinic, Jacksonville, FL Proteomics Unit and NeuroBioGen Lab Memory Clinic R G, L B, G B, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy Department of Clinical Neurological Sciences E F, M J S, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada Division of Neurology G Y R H, and Department of Pathology and Laboratory Medicine I R M, University of British Columbia, Vancouver, Canada Department of Neurology B J K, D S K, R C P, Healthcare Hawkes Bay
    Neurology 81:1332-41. 2013
    ....
  12. pmc Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics
    Jennifer L Whitwell
    Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA
    Brain 135:794-806. 2012
    ..Our analysis suggested that imaging has the potential to be useful to help differentiate C9ORF72 from these other groups at the single-subject level...
  13. doi request reprint Progranulin gene mutation with an unusual clinical and neuropathologic presentation
    Christian 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...
  14. pmc Alzheimer disease-like phenotype associated with the c.154delA mutation in progranulin
    Brendan J Kelley
    Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Arch Neurol 67:171-7. 2010
    ..To characterize a kindred with a familial neurodegenerative disorder associated with a mutation in progranulin (PGRN), with emphasis on the unique clinical features in this kindred...
  15. pmc Prominent phenotypic variability associated with mutations in Progranulin
    Brendan J Kelley
    Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
    Neurobiol Aging 30:739-51. 2009
    ..Some kindreds with PGRN mutations exhibited lateralized topography of degeneration across all affected individuals...
  16. pmc TMEM106B risk variant is implicated in the pathologic presentation of Alzheimer disease
    Nicola J Rutherford
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
    Neurology 79:717-8. 2012
  17. pmc Association between repeat sizes and clinical and pathological characteristics in carriers of C9ORF72 repeat expansions (Xpansize-72): a cross-sectional cohort study
    Marka van Blitterswijk
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    Lancet Neurol 12:978-88. 2013
    ..We assessed whether expansion size is associated with disease severity or phenotype...
  18. pmc Clinical and neuropathologic heterogeneity of c9FTD/ALS associated with hexanucleotide repeat expansion in C9ORF72
    Melissa E Murray
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    Acta Neuropathol 122:673-90. 2011
    ..Further studies are needed to address the molecular mechanism of clinical and pathological heterogeneity of c9FTD/ALS due to mutations in C9ORF72...
  19. pmc Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72
    Bradley F Boeve
    Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA
    Brain 135:765-83. 2012
    ..While variability exists, most cases with this mutation have a characteristic spectrum of demographic, clinical, neuropsychological, neuroimaging and especially neuropathological findings...
  20. pmc Psychosis and hallucinations in frontotemporal dementia with the C9ORF72 mutation: a detailed clinical cohort
    Andrew Kertesz
    Departments of Clinical Neurological Sciences and Pathology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada Department of Neuroscience, Mayo Clinic, Jacksonville, FL
    Cogn Behav Neurol 26:146-54. 2013
    ..To specify the presenting symptoms and clinical course of patients with frontotemporal dementia (FTD) and chromosome 9 open reading frame 72 (C9ORF72) repeat expansion...
  21. pmc Tau pathology in frontotemporal lobar degeneration with C9ORF72 hexanucleotide repeat expansion
    Kevin F Bieniek
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Acta Neuropathol 125:289-302. 2013
    ....
  22. pmc TARDBP mutations in Parkinson's disease
    Sruti Rayaprolu
    Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Parkinsonism Relat Disord 19:312-5. 2013
    ..Our findings widen the phenotypic presentation for the TDP-43 p.N267S substitution and support a possible role for rare TDP-43 mutations presenting with Parkinson's disease...
  23. pmc Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS
    Mariely DeJesus-Hernandez
    Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL 32224, USA
    Neuron 72:245-56. 2011
    ..Our findings indicate that repeat expansion in C9ORF72 is a major cause of both FTD and ALS...
  24. ncbi request reprint Expanded C9ORF72 hexanucleotide repeat in depressive pseudodementia
    Kevin F Bieniek
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida2Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, Minnesota
    JAMA Neurol 71:775-81. 2014
    ..Repeat expansions have also been detected infrequently in other disorders, including Alzheimer disease, dementia with Lewy bodies, and parkinsonian disorders...
  25. pmc Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS
    Tania F Gendron
    Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, 32224, USA
    Acta Neuropathol 126:829-44. 2013
    ..These findings provide mechanistic insight into the pathogenesis of c9FTD/ALS, and have significant implications for therapeutic strategies...
  26. ncbi request reprint Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration
    Jennifer Gass
    Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Hum Mol Genet 15:2988-3001. 2006
    ..Neuropathological examination showed FTLD with ubiquitin-positive cytoplasmic and intranuclear inclusions in all PGRN mutation carriers...
  27. pmc Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members
    NiCole Finch
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Brain 132:583-91. 2009
    ..We propose that plasma GRN levels could be used as a reliable and inexpensive tool to identify all GRN mutation carriers in early-onset dementia populations and asymptomatic at-risk individuals...
  28. pmc Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer's disease
    Mitsuru Shinohara
    1 Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    Brain 137:1533-49. 2014
    ..Region-specific amyloid-β₄₂ accumulation might account for differences in the relative amounts of tau pathology and clinical symptoms in familial and sporadic Alzheimer's disease...
  29. pmc Misregulation of human sortilin splicing leads to the generation of a nonfunctional progranulin receptor
    Mercedes Prudencio
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    Proc Natl Acad Sci U S A 109:21510-5. 2012
    ..Based on these results, we propose a potential mechanism linking misregulation of sortilin splicing with altered PGRN metabolism...
  30. pmc Characterization of a family with c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72
    Rodolfo Savica
    Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA
    Arch Neurol 69:1164-9. 2012
    ..We report the clinical, neuropsychologic, and neuroimaging findings of a family with the C9ORF72 mutation and clinical diagnoses bridging the FTD, parkinsonism, and ALS spectrum...
  31. pmc Altered microRNA expression in frontotemporal lobar degeneration with TDP-43 pathology caused by progranulin mutations
    Jannet Kocerha
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    BMC Genomics 12:527. 2011
    ..Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (PGRN) gene...
  32. pmc Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations
    Christina Sundal
    Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA
    Parkinsonism Relat Disord 19:869-77. 2013
    ..Out of 50 patients, 37 had gait impairments, 8 rigidity, 7 bradykinesia, and 5 resting tremor. Our report emphasizes the presence of atypical Parkinsonism in HDLS due to CSF1R mutations. ..
  33. pmc TMEM106B p.T185S regulates TMEM106B protein levels: implications for frontotemporal dementia
    Alexandra M Nicholson
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA
    J Neurochem 126:781-91. 2013
    ..These findings suggest that low TMEM106B levels might protect against FTLD-TDP in these patients. ..
  34. pmc Profilin-1 mutations are rare in patients with amyotrophic lateral sclerosis and frontotemporal dementia
    Marka van Blitterswijk
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Amyotroph Lateral Scler Frontotemporal Degener 14:463-9. 2013
    ..In conclusion, the p.E117G variant appears to represent a benign polymorphism. PFN1 mutations, in general, are rare in ALS and FTLD-TDP patients...
  35. pmc Length of normal alleles of C9ORF72 GGGGCC repeat do not influence disease phenotype
    Nicola J Rutherford
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    Neurobiol Aging 33:2950.e5-7. 2012
    ..No meaningful association between the repeat length of the normal alleles of the GGGGCC repeat in C9ORF72 and disease phenotype or age at onset was observed in C9ORF72 mutation carriers or nonmutation carriers...
  36. pmc Clinicopathologic variability of the GRN A9D mutation, including amyotrophic lateral sclerosis
    Ashley Cannon
    Departments of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    Neurology 80:1771-7. 2013
    ..We examined the clinical and pathologic phenotypes of GRN mutation carriers with the pathogenic A9D (g.26C>A) missense mutation...
  37. pmc Corticospinal tract degeneration associated with TDP-43 type C pathology and semantic dementia
    Keith A Josephs
    Behavioural Neurology, Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA
    Brain 136:455-70. 2013
    ....
  38. pmc Fus gene mutations in familial and sporadic amyotrophic lateral sclerosis
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA
    Muscle Nerve 42:170-6. 2010
    ..This study demonstrates that the phenotype with FUS mutations extends beyond classical ALS cases. Our findings suggest there are specific clinicogenetic correlations and provide the first detailed neuropathological description...
  39. doi request reprint Clinical and electrophysiologic variability in amyotrophic lateral sclerosis within a kindred harboring the C9ORF72 repeat expansion
    Elizabeth A Coon
    Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Amyotroph Lateral Scler Frontotemporal Degener 14:132-7. 2013
    ..In conclusion, this kindred demonstrates that the presentation of ALS within c9FTD/ALS families may vary considerably and electrophysiologic findings reflect this heterogeneity...
  40. pmc Analysis of the C9orf72 repeat in Parkinson's disease, essential tremor and restless legs syndrome
    Mariely DeJesus-Hernandez
    Department of Neuroscience, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Parkinsonism Relat Disord 19:198-201. 2013
    ..Therefore the C9orf72 hexanucleotide repeat expansion appears to be specific to TDP-43 driven amyotrophic lateral sclerosis and dementia...
  41. pmc An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and Lewy body pathology
    Christian Wider
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    J Neurol Neurosurg Psychiatry 83:424-9. 2012
    ..The study investigates the effects of genetic factors on the pathology of Alzheimer's disease (AD) and Lewy body (LB) diseases, including Parkinson's disease and dementia with Lewy bodies...
  42. pmc Voxel-based morphometry in frontotemporal lobar degeneration with ubiquitin-positive inclusions with and without progranulin mutations
    Jennifer 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...
  43. ncbi request reprint Differential clinicopathologic and genetic features of late-onset amnestic dementias
    Melissa E Murray
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
    Acta Neuropathol 128:411-21. 2014
    ..Pure HpScl and HpScl with concomitant AD occur most often in elderly individuals. ..
  44. ncbi request reprint Progranulin protein levels are differently regulated in plasma and CSF
    Alexandra M Nicholson
    From the Department of Neuroscience A M N, N A F, A W, N J R, R R and Division of Biomedical Statistics and Informatics C S T, Mayo Clinic, Jacksonville, FL and Division of Epidemiology, Department of Health Sciences Research M M M, R O R and Department of Neurology R O R, B F B, D S K, R C P, Mayo Clinic, Rochester, MN
    Neurology 82:1871-8. 2014
    ..We aimed to investigate the relationship between plasma and CSF progranulin (PGRN) levels...
  45. pmc Reduced C9orf72 gene expression in c9FTD/ALS is caused by histone trimethylation, an epigenetic event detectable in blood
    Veronique V Belzil
    Department of Research, Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
    Acta Neuropathol 126:895-905. 2013
    ..Confirming these exciting results using blood from a larger cohort of patients may establish this novel epigenetic event as a biomarker for c9FTD/ALS...
  46. ncbi request reprint Ataxin-2 as potential disease modifier in C9ORF72 expansion carriers
    Marka van Blitterswijk
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    Neurobiol Aging 35:2421.e13-7. 2014
    ..Based on our present findings, we postulate that intermediate ATXN2 repeat lengths may render C9ORF72 expansion carriers more susceptible to the development of MND; further studies are needed, however, to validate our findings...
  47. pmc TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia
    Marka van Blitterswijk
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
    Acta Neuropathol 127:397-406. 2014
    ..These new findings show that the protective effects of TMEM106B are not confined to carriers of GRN mutations and might be relevant for prognostic testing, and as a promising therapeutic target for the entire spectrum of FTLD-TDP. ..
  48. pmc Pathogenicity of exonic indels in fused in sarcoma in amyotrophic lateral sclerosis
    Nicola J Rutherford
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    Neurobiol Aging 33:424.e23-4. 2012
    ..Gly475del) was identified, however in vitro studies did not reveal abnormal localization of p.Gly475del mutant FUS. These findings suggest that not all exonic indels in FUS cause disease...
  49. pmc TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease
    Sruti Rayaprolu
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    Mol Neurodegener 8:19. 2013
    ..With this in mind we set out to assess the genetic association of the Alzheimer's disease-related risk variant in TREM2 (rs75932628, p.R47H) with other related neurodegenerative disorders...
  50. pmc Frontal asymmetry in behavioral variant frontotemporal dementia: clinicoimaging and pathogenetic correlates
    Jennifer L Whitwell
    Department of Radiology, Mayo Clinic, Rochester, MN 55905, USA
    Neurobiol Aging 34:636-9. 2013
    ..These findings therefore suggest that neuroanatomical patterns of frontal lobe atrophy in bvFTD are influenced by specific gene mutations...
  51. pmc Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS
    Peter E A Ash
    Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL 32224, USA
    Neuron 77:639-46. 2013
    ..These findings have significant implications for treatment strategies directed at RAN-translated peptides and their aggregation and the RNA structures necessary for their production...
  52. pmc De novo truncating FUS gene mutation as a cause of sporadic amyotrophic lateral sclerosis
    Mariely DeJesus-Hernandez
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Hum Mutat 31:E1377-89. 2010
    ..S402_P411delinsGGGG) which is predicted to expand a conserved poly-glycine motif. Our findings extend the mutation spectrum in FUS leading to ALS and describe the first de novo mutation in FUS...
  53. pmc Common variant in GRN is a genetic risk factor for hippocampal sclerosis in the elderly
    Dennis W Dickson
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Neurodegener Dis 7:170-4. 2010
    ..Recently, a common genetic variant in the 3' untranslated region (3'UTR) of GRN (rs5848; c.*78C>T) located in a microRNA binding site regulated progranulin expression, and the T-allele was increased in FTLD-TDP compared to controls...
  54. pmc Neuropathological features of corticobasal degeneration presenting as corticobasal syndrome or Richardson syndrome
    Naomi Kouri
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    Brain 134:3264-75. 2011
    ..Atrophy of anterior corpus callosum may be a potential neuroimaging marker to differentiate corticobasal degeneration from progressive supranuclear palsy in patients with Richardson syndrome...
  55. pmc Expression of Fused in sarcoma mutations in mice recapitulates the neuropathology of FUS proteinopathies and provides insight into disease pathogenesis
    Christophe Verbeeck
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    Mol Neurodegener 7:53. 2012
    ..In this paper we report the development of somatic brain transgenic (SBT) mice using recombinant adeno-associated virus (rAAV) to investigate how FUS mutations lead to neurodegeneration...
  56. pmc Similarities between familial and sporadic autopsy-proven progressive supranuclear palsy
    Shinsuke Fujioka
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    Neurology 80:2076-8. 2013
    ..Pathologic findings of PSP are neuronal loss, gliosis, and neurofibrillary tangles in basal ganglia, diencephalon, and brainstem; there is increasing recognition of clinicopathologic variants of PSP.(1.)..
  57. pmc CSF1R mutations link POLD and HDLS as a single disease entity
    Alexandra M Nicholson
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
    Neurology 80:1033-40. 2013
    ..Recently, we reported that mutations in the colony-stimulating factor 1 receptor (CSF1R) gene cause HDLS. In this study, we determined whether CSF1R mutations are also a cause of POLD...
  58. pmc How do C9ORF72 repeat expansions cause amyotrophic lateral sclerosis and frontotemporal dementia: can we learn from other noncoding repeat expansion disorders?
    Marka van Blitterswijk
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA
    Curr Opin Neurol 25:689-700. 2012
    ....
  59. pmc Genome-wide screen identifies rs646776 near sortilin as a regulator of progranulin levels in human plasma
    Minerva M Carrasquillo
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
    Am J Hum Genet 87:890-7. 2010
    ..This finding opens avenues for future research into GRN biology and the pathophysiology of neurodegenerative diseases...
  60. ncbi request reprint Neuropathologic features of frontotemporal lobar degeneration with ubiquitin-positive inclusions with progranulin gene (PGRN) mutations
    Keith 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...
  61. pmc Ataxin-2 repeat-length variation and neurodegeneration
    Owen A Ross
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    Hum Mol Genet 20:3207-12. 2011
    ....
  62. pmc Progressive amnestic dementia, hippocampal sclerosis, and mutation in C9ORF72
    Melissa E Murray
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA
    Acta Neuropathol 126:545-54. 2013
    ....
  63. pmc Sequence variants in eukaryotic translation initiation factor 4-gamma (eIF4G1) are associated with Lewy body dementia
    Shinsuke Fujioka
    Departments of Neurology, Mayo Clinic, Jacksonville, FL, USA
    Acta Neuropathol 125:425-38. 2013
    ..The results suggest that in some patients variants in EIF4G1 can be associated with pathology that has a high likelihood of association with clinical features of dementia with Lewy bodies...
  64. pmc MRS in early and presymptomatic carriers of a novel octapeptide repeat insertion in the prion protein gene
    Eric M McDade
    Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
    J Neuroimaging 23:409-13. 2013
    ..These findings expand the possible diagnostic utility of (1) H MRS in familial prion disorders...
  65. pmc Advances in understanding the molecular basis of frontotemporal dementia
    Rosa Rademakers
    Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL 32224, USA
    Nat Rev Neurol 8:423-34. 2012
    ..In this Review, we highlight recent advances in understanding the molecular aspects of FTD, which will provide the basis for improved patient care through the development of more-targeted diagnostic tests and therapies...
  66. ncbi request reprint Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17
    Matt Baker
    Department of Neuroscience, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
    Nature 442:916-9. 2006
    ..Our results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival...
  67. pmc Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS
    Thomas A Ravenscroft
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    Neurobiol Aging 34:2235.e11-3. 2013
    ..No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS...
  68. pmc Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers
    Claudia Jacova
    From the Division of Neurology, Department of Medicine C J, G Y R H, I T, H L, P S, P B K, A J S, H H F, Department of Physics and Astronomy K D, S M, M G, V S, and Department of Pathology and Laboratory Medicine I R M, University of British Columbia, Vancouver, Canada and Department of Neuroscience M B, R R, Mayo Clinic, Jacksonville, FL
    Neurology 81:1322-31. 2013
    ..In this prospective cohort study, we investigated cerebral glucose metabolism reductions on [(18)F]-fluorodeoxyglucose (FDG)-PET in progranulin (GRN) mutation carriers prior to frontotemporal dementia (FTD) onset...
  69. pmc Progranulin regulates neuronal outgrowth independent of sortilin
    Jennifer Gass
    Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA
    Mol Neurodegener 7:33. 2012
    ..We sought to elucidate this relationship to determine what role SORT1, as a regulator of PGRN levels, plays in modulating PGRN's neurotrophic effects...
  70. pmc MRI characteristics and scoring in HDLS due to CSF1R gene mutations
    Christina Sundal
    Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
    Neurology 79:566-74. 2012
    ..To describe the brain MRI characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS) with known mutations in the colony-stimulating factor 1 receptor gene (CSF1R) on chromosome 5...
  71. pmc Hippocampal sclerosis in the elderly: genetic and pathologic findings, some mimicking Alzheimer disease clinically
    Winnie C Pao
    Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
    Alzheimer Dis Assoc Disord 25:364-8. 2011
    ..Hippocampal sclerosis (HpScl) in the elderly is often associated with neurodegeneration...
  72. pmc Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice
    Ya Fei Xu
    Department of Neuroscience, Mayo Clinic, Jacksonville, Florida 32224, USA
    J Neurosci 30:10851-9. 2010
    ..This TDP-43 transgenic line provides a valuable tool for identifying potential roles of wild-type TDP-43 within the CNS and for studying TDP-43-associated neurotoxicity...
  73. pmc Pallidonigral TDP-43 pathology in Perry syndrome
    Christian Wider
    Department of Neurology, Mayo Clinic, Jacksonville, FL, USA
    Parkinsonism Relat Disord 15:281-6. 2009
    ..This study reports clinical, genetic and neuropathologic investigations of Perry syndrome...
  74. pmc Human genetics as a tool to identify progranulin regulators
    Alexandra M Nicholson
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    J Mol Neurosci 45:532-7. 2011
    ..This review highlights the importance of genetic studies in the context of FTLD and further emphasizes the need for future genetic and cell biology research to continue the effort in finding a cure for progranulin-related diseases...
  75. pmc TARDBP mutation analysis in TDP-43 proteinopathies and deciphering the toxicity of mutant TDP-43
    Tania F Gendron
    Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
    J Alzheimers Dis 33:S35-45. 2013
    ..We discuss the putative harmful consequence of abnormal TDP-43 fragmentation, as well as highlight additional mechanisms of toxicity associated with mutant TDP-43...
  76. pmc Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): a misdiagnosed disease entity
    Christina Sundal
    Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA
    J Neurol Sci 314:130-7. 2012
    ..Definitive diagnosis can be established only by direct brain tissue examination. Familiarity with the clinical presentation and typical neuroimaging findings may be helpful in narrowing the diagnosis...
  77. ncbi request reprint Frontotemporal dementia and parkinsonism associated with the IVS1+1G->A mutation in progranulin: a clinicopathologic study
    Bradley 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'...
  78. pmc Longitudinal modeling of age-related memory decline and the APOE epsilon4 effect
    Richard J Caselli
    Department of Neurology, Mayo Clinic Arizona, Scottsdale, Arizona 85259, USA
    N Engl J Med 361:255-63. 2009
    ..The age at which memory decline diverges among persons who are homozygous for the APOE epsilon4 allele, those who are heterozygous for the allele, and noncarriers is unknown...
  79. ncbi request reprint Atypical motor and behavioral presentations of Alzheimer disease: a case-based approach
    Andrew P Duker
    Department of Neurology, University of Cincinnati, Cincinnati, OH 45267 0525, USA
    Neurologist 18:266-72. 2012
    ..Alzheimer pathology, however, can cause varying clinical syndromes, including both atypical motor and behavioral presentations...
  80. doi request reprint Corticobasal degeneration: a pathologically distinct 4R tauopathy
    Naomi Kouri
    Department of Neuroscience Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
    Nat Rev Neurol 7:263-72. 2011
    ..Progress in biomarker development to differentiate CBD from other disorders has been slow, but is essential in improving diagnosis and in development of disease-modifying therapies...
  81. pmc Clinical characterization of a kindred with a novel 12-octapeptide repeat insertion in the prion protein gene
    Neeraj Kumar
    Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Arch Neurol 68:1165-70. 2011
    ..To report the clinical, electroencephalographic, and neuroradiologic findings in a kindred with a novel insertion in the prion protein gene, PRNP...
  82. pmc Frontotemporal lobar degeneration with TDP-43 proteinopathy and chromosome 9p repeat expansion in C9ORF72: clinicopathologic correlation
    Eileen H Bigio
    Cognitive Neurology and Alzheimer Disease Center, Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
    Neuropathology 33:122-33. 2013
    ....
  83. ncbi request reprint Progressive supranuclear palsy: pathology and genetics
    Dennis 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...
  84. ncbi request reprint Characterization of ubiquitinated intraneuronal inclusions in a novel Belgian frontotemporal lobar degeneration family
    Daniel Pirici
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology VIB8, Institute Born Bunge, University of Antwerp, Belgium
    J Neuropathol Exp Neurol 65:289-301. 2006
    ..Whereas the precise nature of the protein remains elusive, characterization of such familial FTLD-U patients would be helpful in identifying a common denominator in the pathogenesis of familial and the more prevalent sporadic FTLD-U...
  85. ncbi request reprint High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy
    Rosa 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...
  86. ncbi request reprint Tau is central in the genetic Alzheimer-frontotemporal dementia spectrum
    Bart Dermaut
    Department of Molecular Genetics VIB 8, Flanders Interuniversity Institute for Biotechnology, Neurodegenerative Brain Diseases Group, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, B 2610 Antwerpen, Belgium
    Trends Genet 21:664-72. 2005
    ..Together, these studies suggest that AD and FTD are linked in a genetic spectrum of presenile degenerative brain disorders in which tau appears to be the central player...
  87. ncbi request reprint Dose dependent effect of APOE epsilon4 on behavioral symptoms in frontal lobe dementia
    Sebastiaan Engelborghs
    Department of Neurology and Memory Clinic, Middelheim General Hospital, ZNA, Antwerp, Belgium
    Neurobiol Aging 27:285-92. 2006
    ..In conclusion, APOE has disease-specific effects on BPSD in FTD and PDD/DLB patients, given the reported associations of APOE epsilon4 with aggression (FTD) and of APOE epsilon2 with delusions (PDD/DLB)...
  88. ncbi request reprint A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD
    Julie van der Zee
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Brain 129:841-52. 2006
    ..Together, these results strongly suggest that the DR2-DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations...
  89. ncbi request reprint Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21
    Marc Cruts
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Universiteitsplein 1, BE 2610 Antwerpen, Belgium
    Nature 442:920-4. 2006
    ..Furthermore, in a Belgian series of familial FTD patients, PGRN mutations were 3.5 times more frequent than mutations in MAPT, underscoring a principal involvement of PGRN in FTD pathogenesis...
  90. ncbi request reprint Genomic architecture of human 17q21 linked to frontotemporal dementia uncovers a highly homologous family of low-copy repeats in the tau region
    Marc Cruts
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Hum Mol Genet 14:1753-62. 2005
    ..The presence of multiple homologous LCRs in the region predicts that other potentially more complex genomic rearrangements might be underlying FTDU-17...
  91. ncbi request reprint PRNP Val129 homozygosity increases risk for early-onset Alzheimer's disease
    Bart Dermaut
    Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology VIB8, University of Antwerp, Antwerpen, Belgium
    Ann Neurol 53:409-12. 2003
    ..2; 95% CI, 1.4-7.1; p < 0.01). In patients with a positive family history, these risks increased to 2.6 (95% CI, 1.3-5.3; p < 0.01) and 3.5 (95% CI, 1.3-9.3; p = 0.01), respectively...
  92. pmc Gene expression study on peripheral blood identifies progranulin mutations
    Giovanni Coppola
    Department of Neurology, Program in Neurogenetics, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA
    Ann Neurol 64:92-6. 2008
    ..This proof-of-principle report supports the use of gene quantification as diagnostic screen for PGRN mutations and suggests a potential role for progranulin in Alzheimer's disease...
  93. ncbi request reprint The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene
    Ian R A Mackenzie
    Department of Pathology and Laboratory Medicine, University of British Columbia and Vancouver Coastal Health Vancouver, BC, Canada
    Brain 129:3081-90. 2006
    ..These findings suggest that FTD caused by PGRN mutations has a recognizable pathology with the most characteristic feature being ub-ir NII...
  94. pmc A90V TDP-43 variant results in the aberrant localization of TDP-43 in vitro
    Matthew J Winton
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    FEBS Lett 582:2252-6. 2008
    ..Thus, A90V may be a genetic risk factor for FTLD/ALS because it predisposes nuclear TDP-43 to redistribute to the cytoplasm and form pathological aggregates...
  95. ncbi request reprint The molecular genetics and neuropathology of frontotemporal lobar degeneration: recent developments
    Ian R A Mackenzie
    Department of Pathology, Vancouver General Hospital, 855 West 12th Avenue, Vancouver, BC, V5Z 1M9, Canada
    Neurogenetics 8:237-48. 2007
    ..It is anticipated that these discoveries will facilitate the development of new diagnostic tests and therapeutics...
  96. doi request reprint Founder mutation p.R1441C in the leucine-rich repeat kinase 2 gene in Belgian Parkinson's disease patients
    Karen Nuytemans
    Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    Eur J Hum Genet 16:471-9. 2008
    ..Functional data should underlie a conclusion on the pathogenic nature of some mutations that have not been conclusively linked to disease...
  97. pmc novoSNP, a novel computational tool for sequence variation discovery
    Stefan Weckx
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerpen, Belgium
    Genome Res 15:436-42. 2005
    ....
  98. ncbi request reprint Novel APP mutation V715A associated with presenile Alzheimer's disease in a German family
    Marc Cruts
    J Neurol 250:1374-5. 2003
  99. pmc Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample
    Rosa Rademakers
    Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, University of Antwerp, Antwerp, Belgium
    Am J Hum Genet 77:643-52. 2005
    ....
  100. pmc TDP-43 A315T mutation in familial motor neuron disease
    Michael A Gitcho
    Alzheimer s Disease Research Center, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Neurol 63:535-8. 2008
    ..The discovery of a missense mutation in TDP-43 in a family with dominantly inherited motor neuron disease provides evidence of a direct link between altered TDP-43 function and neurodegeneration...
  101. ncbi request reprint Visualization of MAPT inversion on stretched chromosomes of tau-negative frontotemporal dementia patients
    Ilse Gijselinck
    Hum Mutat 27:1057-9. 2006

Research Grants2

  1. Progranulin: Mutation and Regulation in Neurodegenerative disease
    Rosa Rademakers; Fiscal Year: 2009
    ..Unveiling the genetic and molecular pathways regulating PGRN may also reveal novel therapeutic targets that can be exploited for therapeutic actions aimed at delaying the neurodegenerative disease process. ..
  2. Progranulin: Mutation and Regulation in Neurodegenerative disease
    Rosa Rademakers; Fiscal Year: 2010
    ..Unveiling the genetic and molecular pathways regulating PGRN may also reveal novel therapeutic targets that can be exploited for therapeutic actions aimed at delaying the neurodegenerative disease process. ..