Genomes and Genes
Paul G Ince
Affiliation: University of Sheffield
- Neuropathology of vascular cognitive impairment and vascular dementiaPaul G Ince
Neuropathology, Academic Unit of Pathology, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, UK
Int Psychogeriatr 15:71-5. 2003..This mini-review summarizes the authors' views on SVD substrates leading to cognitive decline and proposes priorities for pathological investigations of human cerebrovascular mechanisms leading to cognitive decline...
- Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing StudyFiona E Matthews
Medical Research Council MRC Biostatistics, University of Cambridge, Cambridge, United Kingdom
PLoS Med 6:e1000180. 2009..We report the attributable risks (ARs) for dementia at death for common age-related degenerative and vascular pathologies, and other factors, in the MRC Cognitive Function and Ageing Study (MRC CFAS)...
- Molecular pathology and genetic advances in amyotrophic lateral sclerosis: an emerging molecular pathway and the significance of glial pathologyPaul G Ince
Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK
Acta Neuropathol 122:657-71. 2011....
- Return of the cycad hypothesis - does the amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) of Guam have new implications for global health?P G Ince
Academic Unit of Pathology, Division of Genomic Medicine, University of Sheffield, Sheffield, UK
Neuropathol Appl Neurobiol 31:345-53. 2005..Therefore the pathogenesis of Lytico-Bodig appears still to have most pertinence to the ongoing investigation of the pathogenesis of AD and other tauopathies...
- Corticospinal tract degeneration in the progressive muscular atrophy variant of ALSP G Ince
Neuropathology, Academic Unit of Pathology, Division of Genomic Medicine, Sheffield University, UK
Neurology 60:1252-8. 2003..Examining the unresolved relationship between the lower motor neuron disorder progressive muscular atrophy (PMA) and ALS is important in clinical practice because of emerging therapies...
- Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotypeJulie E Simpson
Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
Neurobiol Aging 32:1795-807. 2011..Our findings implicate astrocyte dysfunction in the pathogenesis of neurodegenerative pathology in the aging brain, and provide a basis for future candidate studies based on specific pathways...
- Epidemiological neuropathology: the MRC Cognitive Function and Aging Study experienceStephen B Wharton
Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
J Alzheimers Dis 25:359-72. 2011....
- C9ORF72 expansions, parkinsonism, and Parkinson disease: a clinicopathologic studyJohnathan Cooper-Knock
Sheffield Institute for Translational Neuroscience, Sheffield Children s NHS Foundation Trust, Western Bank, UK
Neurology 81:808-11. 2013..To determine the histopathologic bases for the observed incidence of parkinsonism in families with C9ORF72 expansions, which typically cause amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia...
- Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology cohortAndrew P Viggars
Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield S102HQ, UK
Neurosci Lett 505:25-30. 2011....
- Microarray RNA expression analysis of cerebral white matter lesions reveals changes in multiple functional pathwaysJulie E Simpson
Academic Units of Pathology, University of Sheffield, Sheffield, UK
Stroke 40:369-75. 2009..Ischemia contributes to their pathogenesis but other mechanisms may contribute. We used RNA microarray analysis with functional pathway grouping as an unbiased approach to investigate evidence for additional pathogenetic mechanisms...
- Unravelling the enigma of selective vulnerability in neurodegeneration: motor neurons resistant to degeneration in ALS show distinct gene expression characteristics and decreased susceptibility to excitotoxicityAlice Brockington
Academic Neurology Unit, Sheffield Institute for Translational Neuroscience SITRAN, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK
Acta Neuropathol 125:95-109. 2013..The findings suggest that reduced susceptibility to excitotoxicity, mediated in part through enhanced GABAergic transmission, is an important determinant of the relative resistance of oculomotor neurons to degeneration in ALS...
- The cellular and molecular pathology of the motor system in hereditary spastic paraparesis due to mutation of the spastin geneStephen B Wharton
Academic Unit of Pathology, University of Sheffield, Sheffield, United Kingdom
J Neuropathol Exp Neurol 62:1166-77. 2003..All 3 cases also demonstrated evidence of tau pathology outside the motor system, suggesting that the neuropathology is not confined to the motor system in spastin-related HSP...
- Decreased alveolar macrophage apoptosis is associated with increased pulmonary inflammation in a murine model of pneumococcal pneumoniaHelen M Marriott
School of Medicine and Biomedical Sciences, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, United Kingdom
J Immunol 177:6480-8. 2006....
- Age, neuropathology, and dementiaGeorge M Savva
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom
N Engl J Med 360:2302-9. 2009..Research in Alzheimer's disease is focused mainly on younger old persons, whereas studies involving very old persons report attenuated relationships between the pathological features of Alzheimer's disease and dementia...
- Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)Laura E Cox
Department of Neuroscience, University of Sheffield, Sheffield, South Yorkshire, United Kingdom
PLoS ONE 5:e9872. 2010..The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis...
- Alzheimer and vascular neuropathological changes associated with different cognitive States in a non-demented sampleBlossom C M Stephan
Department of Public Health and Primary Care, Institute of Public Health, Cambridge, UK
J Alzheimers Dis 29:309-18. 2012..The results highlight the need for rigorous investigation of both neurodegenerative and vascular risks factors in old age...
- The effect of SOD1 mutation on cellular bioenergetic profile and viability in response to oxidative stress and influence of mutation-typeKatie Richardson
Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, United Kingdom
PLoS ONE 8:e68256. 2013..This study highlights bioenergetic defects within a cellular model of ALS and suggests that oxidative stress is not only detrimental to oxygen consumption but also glycolytic flux, which could lead to an energy deficit in the cell. ..
- Alterations of the blood-brain barrier in cerebral white matter lesions in the ageing brainJulie E Simpson
Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK
Neurosci Lett 486:246-51. 2010..However, ZO-1 and occludin were expressed by glial cells throughout the parenchyma of both control white matter and WML, suggesting these TJ proteins may have other functions in the brain...
- Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72Johnathan Cooper-Knock
Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK
Brain 135:751-64. 2012..0005) discriminated C9ORF72 cases strongly from the rest of the cohort. Inclusions in CA4 neurons were not present in non-C9ORF72 cases, indicating that this pathology predicts mutation status...
- Expression of vascular endothelial growth factor and its receptors in the central nervous system in amyotrophic lateral sclerosisAlice Brockington
Academic Neurology Unit and the Academic Unit of Pathology, University of Sheffield, Medical School, Sheffield, U K
J Neuropathol Exp Neurol 65:26-36. 2006....
- Reactive oxygen species regulate neutrophil recruitment and survival in pneumococcal pneumoniaHelen M Marriott
Section of Infection and Inflammation, School of Medicine and Biomedical Sciences, University of Sheffield, LU107, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK
Am J Respir Crit Care Med 177:887-95. 2008..The relative importance of each role remains poorly defined in community-acquired pneumonia...
- Expression of Ki67, PCNA and the chromosome replication licensing protein Mcm2 in glial cells of the ageing human hippocampus increases with the burden of Alzheimer-type pathologyStephen B Wharton
Academic Unit of Pathology, University of Sheffield, Medical School, UK
Neurosci Lett 383:33-8. 2005..A quantitative relationship to the burden of Alzheimer-type pathology suggests that cell-cycle re-entry in glial cells may be important in the pathogenesis of age-related neurodegeneration...
- White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injuryMalee S Fernando
Division of Genomic Medicine, University of Sheffield, United Kingdom
Stroke 37:1391-8. 2006..Direct evidence of ischemia associated with incidental WM lesions (WMLs) has been lacking, and their pathogenesis is unresolved...
- Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neuronsJ Robin Highley
Sheffield Institute for Translational Neuroscience SITRAN, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, United Kingdom
Neuropathol Appl Neurobiol . 2014....
- From molecule to clinic and community for neurodegeneration: research to bridge translational gapsCarol Brayne
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
J Alzheimers Dis 33:S385-96. 2013..They have influenced thinking about future directions, and the cohorts on which the findings are based will continue to provide an important resource for novel areas of research and future health care planning...
- Population studies of sporadic cerebral amyloid angiopathy and dementia: a systematic reviewHannah A D Keage
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
BMC Neurol 9:3. 2009..We searched the literature for prospective population-based epidemiological clinicopathological studies, free of the biases of other sampling techniques, which were used as a comparison...
- Vascular pathologies and cognition in a population-based cohort of elderly peopleMalee S Fernando
Neuropathology, Academic Unit of Pathology, Division of Genomic Medicine, University of Sheffield, E Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, UK
J Neurol Sci 226:13-7. 2004..Using an MRI strategy to image formalin-fixed brain slices, the study shows that white matter lesions (WMLs) are common (94% overall frequency) and are an independent risk factor for dementia using multivariable analysis...
- Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansionsJohnathan Cooper-Knock
1 Sheffield Institute for Translational Neuroscience SITraN, University of Sheffield, 385a Glossop Road, Sheffield S10 2HQ, UK
Brain 137:2040-51. 2014....
- Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosisJanine Kirby
Department of Neuroscience, Faculty of Medicine, Dentistry and Health, University of Sheffield, Medical School, Sheffield, UK
Neurogenetics 11:217-25. 2010..However, all cases had an absence of clinically overt cognitive dysfunction...
- Selective loss of neurofilament expression in Cu/Zn superoxide dismutase (SOD1) linked amyotrophic lateral sclerosisFiona M Menzies
Academic Neurology Unit and Academic Unit of Pathology, The Medical School, University of Sheffield, South Yorkshire, UK
J Neurochem 82:1118-28. 2002..These data suggest that NFL mRNA reductions are common to SALS and FALS patients, and that cells and mice expressing mutant SOD1 may enable us to characterize the molecular mechanism(s) responsible for the loss of neurofilament mRNA...
- Mitochondrial involvement in amyotrophic lateral sclerosisFiona M Menzies
Department of Neurology, E Floor, Medical School, Royal Hallamshire Hospital, University of Sheffield, Beech Hill Road, S10 2RX, UK
Neurochem Int 40:543-51. 2002..The way in which the involvement of mitochondria fits with other aetiological hypotheses for ALS will also be discussed...
- Alveolar macrophage apoptosis contributes to pneumococcal clearance in a resolving model of pulmonary infectionDavid H Dockrell
Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Sciences, Sheffield, United Kingdom
J Immunol 171:5380-8. 2003..These results suggest that AM play a key role in clearance of bacteria from the lung during subclinical infection and that induction of AM apoptosis contributes to the microbiologic host defense against pneumococci...
- Quantitative assessment of AMPA receptor mRNA in human spinal motor neurons isolated by laser capture microdissectionP R Heath
Academic Unit Neurology, Division of Genomic Medicine, Medical School, University of Sheffield, UK
Neuroreport 13:1753-7. 2002..Thus, it is likely that human spinal motor neurons express a proportion of Ca2+-permeable AMPA receptors which may contribute to the selective vulnerability of these cells in amyotrophic lateral sclerosis...
- Apoptosis in amyotrophic lateral sclerosis: a review of the evidenceS Sathasivam
Department of Neurology, University of Sheffield, Sheffield, UK
Neuropathol Appl Neurobiol 27:257-74. 2001..An understanding of the mechanism of programmed cell death in ALS may provide important clues for areas of potential therapeutic intervention for neuroprotection in this devastating condition...
- Population variation in glial fibrillary acidic protein levels in brain ageing: relationship to Alzheimer-type pathology and dementiaS B Wharton
Academic Unit of Pathology, University of Sheffield Medical School, Sheffield, UK
Dement Geriatr Cogn Disord 27:465-73. 2009..The cellular pathology of astrocytes in brain ageing and their role in modulating the brain's response to neurodegenerative pathology remain incompletely understood...
- Mutations in VAPB are not associated with sporadic ALSJ Kirby
Academic Neurology Unit, University of Sheffield, School of Medicine and Biomedical Sciences, Sheffield, UK
Neurology 68:1951-3. 2007
- White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responsesJ E Simpson
Academic Unit of Pathology, University of Sheffield Medical School, Sheffield S10 2RX, UK
Neuropathol Appl Neurobiol 33:410-9. 2007....
- Hippocampal tau pathology is related to neuroanatomical connections: an ageing population-based studyG Lace
Academic Unit of Pathology, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK
Brain 132:1324-34. 2009..These stages were significantly associated with dementia, and may provide a clinically useful tool in the clinico-pathological assessment of dementia and mild cognitive impairment...
- A brief history of tau: the evolving view of the microtubule-associated protein tau in neurodegenerative diseasesG L Lace
Neuropathology Group, Academic Unit of Pathology, University of Sheffield Medical School, Sheffield, UK
Clin Neuropathol 26:43-58. 2007..By examining the evolution of research on tau, related to advances in technology and the emergence of new diseases, the future developments needed to resolve remaining issues in the tau-story may be discerned...
- Demystifying lobar degenerations: tauopathies vs GehrigopathiesPaul G Ince
Neurology 66:8-9. 2006
- Glial proliferation and metabotropic glutamate receptor expression in amyotrophic lateral sclerosisJohanna M H Anneser
Department of Neurology, Ludwig Maximilians University, Klinikum Grosshadern, Munich, Germany
J Neuropathol Exp Neurol 63:831-40. 2004..Taken together, our data suggest that stimulation of glial mGluRs through mediators present in the CSF may contribute to glial proliferation and astrogliosis in ALS...
- Screening of the regulatory and coding regions of vascular endothelial growth factor in amyotrophic lateral sclerosisAlice Brockington
Neurogenetics 6:101-4. 2005
- Large-scale pathways-based association study in amyotrophic lateral sclerosisDalia Kasperaviciute
Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UK
Brain 130:2292-301. 2007..It is reliable for large scale genotyping studies of diseases such as ALS, where DNA sample collections are limited because of low disease prevalence and short survival time...
- 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...
- 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...
- Dementia with Lewy bodies: a comparison of clinical diagnosis, FP-CIT single photon emission computed tomography imaging and autopsyZuzana Walker
University College London and Royal Free Hospitals, London, UK
J Neurol Neurosurg Psychiatry 78:1176-81. 2007....
- Differential expression of mGluR5 in human lumbosacral motoneuronsJohanna M H Anneser
Department of Neurology, Ludwig Maximilians University, Klinikum Grosshadern, Marchioninistr 15, 81377 Munich, Germany
Neuroreport 15:271-3. 2004..These results are in accordance with previous findings in rat and strengthen the hypothesis that mGluR expression may provide a possible clue to the selective vulnerability in ALS...