Genomes and Genes
Eileen H Bigio
Affiliation: Northwestern University
- Genetic modifiers in carriers of repeat expansions in the C9ORF72 geneMarka van Blitterswijk
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA
Mol Neurodegener 9:38. 2014..Substantial phenotypic heterogeneity has been described in patients with these expansions. We set out to identify genetic modifiers of disease risk, age at onset, and survival after onset that may contribute to this clinical variability...
- TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's diseaseSruti 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...
- Frontotemporal lobar degeneration with TDP-43 proteinopathy and chromosome 9p repeat expansion in C9ORF72: clinicopathologic correlationEileen 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....
- Making the diagnosis of frontotemporal lobar degenerationEileen H Bigio
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Arch Pathol Lab Med 137:314-25. 2013..The 2 major categories of pathologic FTLD are tauopathies (FTLD-tau) and ubiquitinopathies (FTLD-U). Pick disease is one of the FTLD-tau subtypes and is termed FTLD-tau (PiD)...
- TDP-43 variants of frontotemporal lobar degenerationEileen H Bigio
Department of Pathology and Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
J Mol Neurosci 45:390-401. 2011..In this paper, FTLD-TDP pathologic sub-types will be described, and examples of each sub-type will be shown, and implications for future research will be discussed...
- Synapse loss is greater in presenile than senile onset Alzheimer disease: implications for the cognitive reserve hypothesisEileen H Bigio
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA
Neuropathol Appl Neurobiol 28:218-27. 2002..The differences in synapse loss and Alzheimer-type pathology in presenile and senile onset AD support the hypothesis that 'cognitive reserve' protects the human brain from neurodegenerative disease...
- TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer diseaseEileen H Bigio
Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Acta Neuropathol 120:43-54. 2010..Furthermore, medial temporal TDP-43 pathology is more tightly linked to HS than to clinical phenotype. These findings challenge the current notions about clinicopathologic correlation, especially about the role of multiple pathologies...
- Update on recent molecular and genetic advances in frontotemporal lobar degenerationEileen H Bigio
Department of Pathology, Cognitive Neurology and Alzheimer Disease Center, Northwestern University Feinberg School of Medicine, 710 N Fairbanks Court, Chicago, IL 60611, USA
J Neuropathol Exp Neurol 67:635-48. 2008..This review highlights the neuropathologic features and the most important discoveries of the last 2 years and places these findings into the historical context of FTLD...
- Synapse loss may be a minor contributor to decreased regional cerebral blood flow in Alzheimer diseaseEileen H Bigio
Department of Pathology, Northwestern University Medical School, Chicago, Ill 60611, USA
Dement Geriatr Cogn Disord 15:72-8. 2003..The results of this study suggest that synapse loss may be a minor contributor to the decreased rCBF observed in AD...
- Differential involvement of optineurin in amyotrophic lateral sclerosis with or without SOD1 mutationsHan Xiang Deng
Division of Neuromuscular Medicine, Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
Arch Neurol 68:1057-61. 2011..Mutations in optineurin have recently been linked to amyotrophic lateral sclerosis (ALS)...
- Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementiaHan Xiang Deng
Division of Neuromuscular Medicine, Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
Nature 477:211-5. 2011....
- Alzheimer and frontotemporal pathology in subsets of primary progressive aphasiaMarsel Mesulam
Cognitive Neurology and Alzheimer s Disease Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Ann Neurol 63:709-19. 2008..To identify predictors of Alzheimer's disease (AD) versus frontotemporal lobar degeneration pathology in primary progressive aphasia (PPA), and determine whether the AD pathology is atypically distributed to fit the aphasic phenotype...
- Gene expression analysis of frontotemporal lobar degeneration of the motor neuron disease type with ubiquitinated inclusionsManjari Mishra
Cognitive Neurology and Alzheimer Disease Center, Northwestern University, Feinberg School of Medicine, 320 East Superior St, Chicago, IL, 60611, USA
Acta Neuropathol 114:81-94. 2007..Our findings point to specific gene-linked-pathways which may be influenced by neurodegenerative disease process and may be targeted for further exploration...
- FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosisHan Xiang Deng
Division of Neuromuscular Medicine, Davee Department of Neurology and Clinical Neurosciences, Chicago, IL 60611, USA
Ann Neurol 67:739-48. 2010..The pathogenic mechanism of the mutant FUS-mediated ALS and potential roles of FUS in non-FUS ALS remain to be investigated...
- TAR DNA-binding protein 43 immunohistochemistry reveals extensive neuritic pathology in FTLD-U: a midwest-southwest consortium for FTLD studyKimmo J Hatanpaa
Department of Pathology, University of Texas Southwestern School of Medicine, Dallas, Texas 75390, USA
J Neuropathol Exp Neurol 67:271-9. 2008..Moreover, assessment of abnormalities in both the hippocampus and frontal cortex may be diagnostically important in FTLD-U...
- Tau nitration occurs at tyrosine 29 in the fibrillar lesions of Alzheimer's disease and other tauopathiesMatthew R Reynolds
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
J Neurosci 26:10636-45. 2006..Collectively, our findings provide the first direct evidence that site-specific tau nitration is linked to the progression of the neurodegenerative tauopathies...
- Calpain-mediated tau cleavage: a mechanism leading to neurodegeneration shared by multiple tauopathiesAdriana Ferreira
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
Mol Med 17:676-85. 2011..Collectively, these data suggest that the mechanism underlying the generation of the 17-kDa neurotoxic tau fragment might be part of a conserved pathologic process shared by multiple tauopathies...
- Asymmetry and heterogeneity of Alzheimer's and frontotemporal pathology in primary progressive aphasiaM Marsel Mesulam
Cognitive Neurology and Alzheimer s Disease Centre, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA
Brain 137:1176-92. 2014..Revisions of criteria for logopenic primary progressive aphasia are proposed to address these challenges. ..
- National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approachThomas J Montine
Department of Pathology, University of Washington School of Medicine, Box 359791, Seattle, WA 98104, USA
Acta Neuropathol 123:1-11. 2012..Recommendations also are made for the minimum sampling of brain, preferred staining methods with acceptable alternatives, reporting of results, and clinico-pathologic correlations...
- Detection of protein aggregation in neurodegenerative diseasesHan Xiang Deng
Division of Neuromuscular Medicine, Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Methods Mol Biol 793:259-72. 2011..Using this method, we successfully detected some protein aggregates that escaped detection when other antigen-retrieval methods were employed...
- 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...
- West Nile virus encephalomyelitis with polio-like paralysis & nigral degenerationKristian T Schafernak
Division of Neuropathology, Northwestern University Feinberg School of Medicine, 710 N Fairbanks Court, Olson 3 459, Chicago, Illinois 60611, USA
Can J Neurol Sci 33:407-10. 2006..Movement disorders have also been described...
- Conversion to the amyotrophic lateral sclerosis phenotype is associated with intermolecular linked insoluble aggregates of SOD1 in mitochondriaHan Xiang Deng
Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Tarry Building, Room 13 715, 303 East Chicago Avenue, Chicago, IL 60611, USA
Proc Natl Acad Sci U S A 103:7142-7. 2006..Importantly, rational therapy based on these observations can now be developed and tested...
- Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literaturePeter T Nelson
Sanders Brown Center on Aging, Department of Pathology, University of Kentucky, Lexington 40536 0230, USA
J Neuropathol Exp Neurol 71:362-81. 2012..Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles...
- Alterations of Ca²⁺-responsive proteins within cholinergic neurons in aging and Alzheimer's diseaseDavid Riascos
Cognitive Neurology and Alzheimer s Disease Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
Neurobiol Aging 35:1325-33. 2014..Substantial age- and AD-related alterations in Ca(2+)-sensing proteins most likely contribute to selective vulnerability of BFCN to degeneration in AD...
- Pineal chordoid meningioma complicated by repetitive hemorrhage during pregnancy: case report and literature reviewKyung Hwa Lee
Department of Pathology, Northwestern University McGaw Medical Center, Chicago, Illinois 60611, USA
Neuropathology 33:192-8. 2013..Additionally, there was abundant lymphoplasmacytic infiltration within the tumor. The details of this case are presented with a review of the literature...
- Tau truncation during neurofibrillary tangle evolution in Alzheimer's diseaseAngela L Guillozet-Bongaarts
Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, 303 E Chicago Avenue, Chicago, IL 60611, USA
Neurobiol Aging 26:1015-22. 2005....
- Nuclear Carrier and RNA Binding Proteins in Frontotemporal Lobar Degeneration associated with Fused in Sarcoma (FUS) pathological changesYvonne S Davidson
Mental Health and Neurodegeneration Research Group, Faculty of Human and Medical Sciences, University of Manchester, Manchester, UK Northwestern CNADC Neuropathology Core, Northwestern University Feinberg School of Medicine, Chicago, USA Department of Neuropathology, Walton Centre for Neurology and Neurosurgery, Liverpool, UK Neuropathology Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK Institute for Ageing and Health, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK Departments of Neurology and Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA Cerebral Function Unit, Greater Manchester Neuroscience Centre, Salford Royal Foundation Trust, UK
Neuropathol Appl Neurobiol . 2012..2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society...
- Neuronal ubiquitinated intranuclear inclusions in familial and non-familial frontotemporal dementia of the motor neuron disease type associated with amyotrophic lateral sclerosisEileen H Bigio
Northwestern Cognitive Neurology and Alzheimer Disease Center, and Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA
J Neuropathol Exp Neurol 63:801-11. 2004..In addition, the current study confirms that Ub-INIs are found in familial FTD-MND-type, but also extends the presence of Ub-INIs to familial FTD-MND (with concomitant ALS), and probably also to non-familial FTD-MND-type...
- 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...
- Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosisNicola J Rutherford
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, United States of America
PLoS Genet 4:e1000193. 2008....
- Lateralization on neuroimaging does not differentiate frontotemporal lobar degeneration from Alzheimer's diseaseAnne M Lipton
Alzheimer s Disease Centers at The University of Texas Southwestern Medical Center, Dallas, Tex, USA
Dement Geriatr Cogn Disord 17:324-7. 2004..Three of 4 FTLD cases had lateralized atrophy on CT. For the AD cases, 10/17 SPECTs, 2/7 MRIs, and 1/9 CTs showed lateralized findings. Of the neuroimaging modalities utilized, SPECT was the most sensitive in detecting lateralization...
- TAR DNA-binding protein-43 in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer diseaseEileen H Bigio
Acta Neuropathol 116:135-40. 2008
- TDP-43 A315T mutation in familial motor neuron diseaseMichael 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...
- 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...
- Frontotemporal lobar degeneration with motor neuron disease-type inclusions predominates in 76 cases of frontotemporal degenerationAnne M Lipton
Department of Neurology, University of Texas Southwestern Medical School, 5323 Harry Hines Blvd, Dallas, TX 75390 9129, USA
Acta Neuropathol 108:379-85. 2004..Only eight (11%) were classified as Pick's disease. Several cases originally designated as DLDH could be reclassified as FTLD-MND-type based on current recommendations for classification of FTD...
- Synaptic targeting by Alzheimer's-related amyloid beta oligomersPascale N Lacor
Neurobiology and Physiology Department, Northwestern University, Evanston, Illinois 60208, USA5
J Neurosci 24:10191-200. 2004..Results suggest the hypothesis that targeting and functional disruption of particular synapses by Abeta oligomers may provide a molecular basis for the specific loss of memory function in early AD...
- Mutation analysis of patients with neuronal intermediate filament inclusion disease (NIFID)Parastoo Momeni
Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, Building 35 Room 1A1010 35 Convent Drive, Bethesda, MD 20892, USA
Neurobiol Aging 27:778.e1-778.e6. 2006..To determine the molecular genetic contribution to this disease we performed a mutation analysis of all type IV neuronal IF, SOD1 and NUDEL genes in cases of NIFID and unaffected control cases. We found no pathogenic variants...
- Letter to the editorNigel J Cairns
J Neuropathol Exp Neurol 65:97; author reply 97-8. 2006
- An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodiesRohan de Silva
Reta Lila Weston Institute of Neurological Studies, University College London, Windeyer Building, 46 Cleveland St, W1T 4JF, London, UK
Acta Neuropathol 111:329-40. 2006..The use of such tau isoform specific antibodies may refine pathological criteria underpinning FTLD...
- Tc-99m HMPAO SPECT in the differential diagnosis of the dementias with histopathologic confirmationFrederick J Bonte
Nuclear Medicine Center, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9061, USA
Clin Nucl Med 31:376-8. 2006..The purpose of this study is to determine the value of Tc-99m HMPAO SPECT in the diagnosis of the dementias, with particular reference to Alzheimer disease...
- Monoclonal antibodies that target pathological assemblies of AbetaMary P Lambert
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA
J Neurochem 100:23-35. 2007....
- Cognitive impairment, frontotemporal dementia, and the motor neuron diseasesMichael J Strong
Department of Clinical Neurological Sciences and the Robarts Research Institute, London, Ontario, Canada
Ann Neurol 54:S20-3. 2003
- Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementiaOdity Mukherjee
Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA
Hum Mutat 29:512-21. 2008....
- Phenotypic variability associated with progranulin haploinsufficiency in patients with the common 1477C-->T (Arg493X) mutation: an international initiativeRosa 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...
- TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusionsNigel J Cairns
MRCPath, Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, St Louis, MO 63110, USA
Am J Pathol 171:227-40. 2007....
- Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar DegenerationNigel J Cairns
Department of Neurology, Washington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St Louis, MO, 63110, USA
Acta Neuropathol 114:5-22. 2007..These criteria will be of value to the practicing neuropathologist and provide a foundation for clinical, clinico-pathologic, mechanistic studies and in vivo models of pathogenesis of FTLD...
- Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutationsIan R A Mackenzie
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Ann Neurol 61:427-34. 2007..We recently identified TDP-43 as the major pathological protein in sporadic ALS. In this study, we investigated TDP-43 in a larger series of ALS cases (n = 111), including familial cases with and without SOD1 mutations...
- Alzheimer's disease-type neuronal tau hyperphosphorylation induced by A beta oligomersFernanda G De Felice
Department of Neurobiology and Physiology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA
Neurobiol Aging 29:1334-47. 2008..A beta oligomers have been increasingly implicated as the main neurotoxins in AD, and the current results provide a unifying mechanism in which oligomer activity is directly linked to tau hyperphosphorylation in AD pathology...
- Neuronal intranuclear inclusions are ultrastructurally and immunologically distinct from cytoplasmic inclusions of neuronal intermediate filament inclusion diseaseSabrina Mosaheb
Electron Microscope Division, Sussex Centre for Advanced Microscopy, School of Life Sciences, University of Sussex, Brighton, UK
Acta Neuropathol 110:360-8. 2005..These observations indicate that abnormal protein aggregation follows separate pathways in different neuronal compartments of NIFID...
- alpha-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseasesNigel J Cairns
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3600 Spruce Street, Philadelphia, PA 19104 4283, USA
Acta Neuropathol 108:213-23. 2004..The discovery of alpha-internexin in neuronal cytoplasmic inclusions implicates novel mechanisms of pathogenesis in NIFID and other neurological diseases with pathological filamentous neuronal inclusions...
- Can alzheimer's disease and dementias with Lewy bodies be distinguished clinically?Myron F Weiner
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75390 9070, USA
J Geriatr Psychiatry Neurol 16:245-50. 2003..LB dementias differed from AD at initial evaluation, with more frequent hallucinations and delusions, EPSs, and seizures, and longitudinally in neuroleptic sensitivity, but the data did not distinguish LBV from DLBD...
- Identification of a novel risk locus for progressive supranuclear palsy by a pooled genomewide scan of 500,288 single-nucleotide polymorphismsStacey Melquist
Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA
Am J Hum Genet 80:769-78. 2007..Since DNA damage and lysosomal dysfunction have been implicated in aging and neurodegenerative processes, both genes are viable candidates for conferring risk of disease...