Professor Paul G Ince

Prof Paul Ince

Professor of Neuropathology


Head of Department

Consultant Neuropathologist, Sheffield Teaching Hospitals NHS Foundation Trust

Director of the Sheffield Brain Tissue Bank

Academic Neurology Unit
Department of Neuroscience
Sheffield Institute for Translational Neuroscience
University of Sheffield
Room B35
385a Glossop Road
Sheffield
S10 2HQ

Tel: +44 (0)114 22 22234
Fax: +44 (0)114 22 22290
Email:p.g.ince@sheffield.ac.uk

Secretary: Bev Carter
Tel: +44 (0)114 22 22295
Email:bev.carter@sheffield.ac.uk


Appointments

  • 1989-2000 MRC Clinical Scientist, Senior Lecturer in Neurochemical Pathology (University of Newcastle upon Tyne) and Honorary Consultant Neuropathologist
  • 1982-1989 Lecturer in Pathology, University of Newcastle upon Tyne
  • 1979-1982 Demonstrator in Pathology, University of Newcastle upon Tyne


Editorial activity

  • Executive Editor: Neuropathology and Aplied Neurobiology
  • Editorial Board Member: Dementia and Geriatric Cognitive Disorders; Journal of Neuropathology and Experimental Neurology


Professional Academic Activity

  • Secretary to the British Neuropathological Society (2000-2004)
  • MRC Panel of Clinical Research Fellowship Training Referees (2000 - present)
  • Motor Neurone Disease Association Research Advisory Panel (2000 - 2004)
  • Parkinson's Disease Society Research Advisory Panel (2003 - present)
  • Alzheimer's Society Scientific and Medical Advisory Panel (2001 - present)
  • Chairman: Neuropathology and Brain Banking Clinical Studies Group, Dmentia and Neurodegenerative Disease Research Network, UKCRN (2007 - present)
  • Secretary General: European Confederation of Neuropathological Societies (From January 2008)
  • MRC Neurosciences and Mental Health Board (From April 2008)


Research

Prof Ince’s main research interests are in brain ageing, neurodegeneration, vascular disease and motor system disorders. He is the lead neuropathologist for the MRC Cognitive Function and Ageing Study (CFAS) and has collaborated with Prof Shaw on human neuropathology studies of ALS and other motor disorders for more than 20 years. The CFAS Neuropathology study has delivered a series of high profile papers defining the relationship between brain pathology and cognition in a large ageing population-based cohort. Project work has included characterisation of the pathology and pathophysiology of age-related white matter lesions in the human brain, the prevalence and significance of synucleinopathy in the elderly and many other facets of brain ageing and dementia. The CFAS project has been continuously funded by MRC for 26 years.
Professor Ince directs the Sheffield Brain Tissue Bank (SBTB) that forms a central resource for human neuroscience research in Sheffield based on the characterisation of human brain tissue donated by patients and the public. SBTB has underpinned numerous studies in ALS/MND and other human motor system diseases.

ALS/MND:
His current involvement is centred on molecular pathological studies of human ALS tissue and transgenic models, and the clinical pathology of ALS variants and familial ALS. Professor Ince administers and manages the Sheffield Brain Tissue Bank.

MRC Cognitive Function and Ageing Study:
MRC CFAS is currently funded as an MRC Co-operative Group. Prof Ince is a Principal Investigator in the Co-op and leads, or collaborates with, Component Project Grants in Sheffield to extend the pathological studies to vascular pathology, inflammatory markers of brain injury, astrogliosis and tauopathy, and synucleinopathy. CFAS is a longitudinal multidisciplinary population-based study of health and frailty in the elderly. It has generated data on cognitive function and depression in the elderly providing a unique opportunity to develop "epidemiological neuropathology" in an elderly cohort including cognitively normal individuals.

  1. Prof Ince leads pathological studies of biochemical indices of brain pathology in the CFAS donor cohort and use of new pathology protocols (BrainNET Europe), measures of oligomeric amyloid content, biochemical indices of neuronal and synaptic depletion, and measures of innate brain immune activation, attempting to improve the predictive power of pathological modelling of cognitive outcomes in later life.
  2. The pathology and pathogenesis of white matter lesions in brain ageing with a particular focus cerebral microvascular disease.

Recent Publications

Books and Book chapters:

Ince P.G., Perry R.H., Perry E.K. Dementia with Lewy Bodies: Neuropathology and Neurochemistry. In: Dementia 2nd Ed. Eds: O¡`Brien J, Ames D., Burns A. Chapman and Hall

Ince PG, Wharton SB. Cytopathology of the Motor Neuron. In: Motor Neuron and Related Diseases. Handbook of Clinical Neurology Series, 3rd Edition Eds. Eisen AA, Shaw PJ. Elsevier, Amsterdam. Vol 82 pp89-120. 2007

Ince P, Wharton S, Shaw P, Clark B, Revesz T, Holton J. Diseases of movement, and system degenerations. Chapter 13. In: Greenfield´s Neuropathology, 8th Ed. Eds: Ellison D, Louis D, Love S. Arnold, London (in Press) (2007)


Selected research papers:

McKeith IG., Ballard CG., Perry RH., Ince PG., O'Brien JT., Neill D., Lowery K., Jaros E., Barber R., Thompson P., Swann A., Fairbairn AF., Perry EK. Prospective validation of consensus criteria for the diagnosis of dementia with Lewy bodies. Neurology. 54: 1050-8 (2000)

White KD. Ince PG. Lusher M. Lindsey J. Cookson M. Bashir R. Shaw PJ. Bushby KM. Clinical and pathologic findings in hereditary spastic paraparesis with spastin mutation. Neurology. 55: 89-94 (2000)

Neuropathology Group of the MRC CFAS [writing committee: Esiri MM, Matthews F, Brayne C, Ince PG] Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet 357: 169-175 (2001)

Curtis, A.R.J., Fey, C., Morris, C.M., Bindoff, L.A., Ince, P.G., Chinnery, P.F., Coulthard, A., Jackson, M.J., Jackson, A.P., McHale, D.P., Hay, D., Barker, W.A., Markham, A.F., Bates, D., Curtis, A., Burn, J. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset neurodegeneration. Nature Genetics 28: 327-334 (2001)

Cottrel, D.A., Ince, P.G., Wardell, T.M., Turnbull, D.M., Johnson, M.A. Accelerated ageing changes in the choroids plexus of a case with multiple mitochondrial DNA deletions. Neuropathol Appl Neurobiol 27: 206-215 (2001)
Munch C., Penndorf A., Schwalenstocker B., Troost D., Ludolph A.C., Ince P., Meyer T., Impaired RNA splicing of 5'-regulatory sequences of the astroglial glutamate transporter EAAT2 in human astrocytoma. J Neurol Neurosurg Psychiatry. 71:675-8 (2001).

Cottrell D.A., Blakely E.L., Johnson M.A., Ince P.G., Turnbull D.M. Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD. Neurology 57:260-4 (2001).

Banner S.J., Fray A.E., Ince P.G., Steward M., Cookson M.R., Shaw P.J. The expression of the glutamate re-uptake transporter Excitatory Amino Acid Transporter 1 (EAAT1) in the normal human CNS and in motor neurone disease: an immunohistochemical study. Neuroscience 109: 27-44 (2002)

Menzies F.M., Grierson, A.J., Cookson M.R., Heath P.R., Tomkins J., Figlewicz D.A., Ince P.G., Shaw P.J. Selective loss of neurofilament expression in Cu/Zn Superoxide dismutase (SOD1) linked amyotrophic lateral sclerosis. J Neurochem 82:118-128 (2002)

Walker Z., Costa D.C, Walker R.W.H., Shaw K., Gacinovic S., Stevens T., Livingston G, Ince P.G., McKeith I.G., Katona CLE. Differentiation of dementia with Lewy bodies from Alzheimer's disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry 73:134-40 (2002)
Heath P.R., Tomkins J., Ince P.G., Shaw P.J. Quantitative assessment of AMPA receptor mRNA in human spinal motor neurons isolated by laser capture microdissection. Neuroreport 13: 1753-7 (2002)

Cottrell D.A., Borthwick G.M., Johnson M.A., Ince P.G., Turnbull D.M. The role of cytochrome C oxidase deficient hippocampal neurones in Alzheimer´s disease. Neuropathol Appl Neurobiol 28: 390-6 (2002)

Ince P.G., Evans J., Knopp M., Forster G, Wharton S., Shaw P.J. Corticospinal tract degeneration in the progressive muscular atrophy variant of ALS. Neurology 60: 1252-8 (2003)

Wharton S.B, McDermott C.J, Grierson A.J., Wood J.D., Gelsthorpe C., Ince P.G., Shaw P.J. The cellular and molecular pathology of the motor system in hereditary spastic paraparesis due to mutation of the spastin gene J Neuropath Exp Neurol 62:1166-77 (2003)

Fernando MS, O´Brien JT, Perry RH, McMeekin W, Jaros E, Slade J, Golkhar A, English PT, Barber R, Kalaria RN, Ince P.G.,on behalf of the Neuropathology Group of MRC CFAS. Direct comparison of magnetic resonance imaging of fixed brain tissue and the neuropathology of cerebral white matter in the elderly brain. Neuropathol Appl Neurobiol 30: 385-395 (2004)

Fernando MS, Ince P.G. on behalf of the Neuropathology Group of MRC CFAS. Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci, 226: 13-7 (2004)

Wharton SB, Williams GH, Stoeber K, Gelsthorpe CH, Baxter L, Johnson AL, Ince PG. Expression of Ki67, PCNA and chromosome replication licensing protein Mcm2 in glial cells of the ageing human hippocampus increases with the burden of Alzheimer-type pathology Neurosci Lett 383: 33-8 (2005)

Borthwick GM, Ince PG, Taylor RW, Walls TJ, Tonska K, Taylor GA, Shaw PJ, Turnbull DM Motor neurone disease (MND) phenotype in a patient with a mitochondrial tRNAIle (4274T>C) mutation. Ann Neurol 59; 570-4 (2006)

Brockington A, Wharton SB, Fernando M, Gelsthorpe C, Baxter L, Ince PG, Lewis CE, Shaw PJ. Expression of vascular endothelial growth factor and its receptors in the central nervous system in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 65; 26-36 (2006)

Fernando MS, Simpson JE, Matthews F, Brayne C, Lewis C, Barber R, Kalaria RN, Forster G, Esteves F, Wharton SB, Shaw PJ, O´Brien JT, Ince PG (on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group) White matter lesions in an unselected cohort of the elderly: Molecular pathology suggests origin from chronic hypoperfusion injury. Stroke 37; 1391-1398 (2006)

Lewis H, Beher D, Cookson N, Oakley A, Piggot M, Morris CM, Jaros E, Perry R, Ince P, Kenny RA, Ballard CG, Shearman MS, Kalaria RN. Quantification of Alzheimer pathology in ageing and dementia: age-related accumulation of amyloid-β(42) peptide in vascular dementia. Neuropathol Appl Neurobiol 32: 103-18 (2006)
Thomas AJ, Hendriksen M, Piggott M, Ferrier IN, Perry EJ, Ince P, O´Brien JT. A study of the serotonin transporter in the prefrontal cortex in late-life depression and Alzheimer´s disease with and without depression. Neuropathol Appl Neurobiol 32; 296-303 (2006)

Wood-Allum CA, Barber SC, Kirby J, Heath P, Holden H, Mead R, Higginbottom A, Allen S, Beaujeux T, Alexson SE, Ince PG, Shaw PJ. Impairment of mitochondrial anti-oxidant defence in SOD1-related motoneuron injury and amelioration by ebselen. Brain 129: 1693-1709 (2006)

Parkinson N, Ince PG, Smith MO, Highley R, Skibinski G, Andersen PM, Morrison KE, Pall HS, Hardiman O, Collinge J, Shaw PJ, Fisher EM; MRC Proteomics in ALS Study; FReJA Consortium. ALS phenotypes associated with mutations in CHMP2B (charged multivesicular body protein 2B). Neurology 67: 1074-7 (2006)

Walker Z, Jaros E, Walker RWH, Lee L, Costa DC, Livingston G, Ince PG, Perry R, McKeith I. Katona CLE Dementia with lewy bodies: A comparison of clinical diagnosis, FP-CIT SPECT imaging and autopsy J Neurol Neurosurg Psychiatry jnnp.2006.110122 (2007)

Simpson JE, Clark L, Ince PG., Forster G, O´Brien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Lewis CE, Wharton SB on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. The cellular pathology of periventricular and deep white matter lesions in the ageing brain: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol Appl Neurobiol 33; 410-19 (2007)

Kirby J, Hewamadduma CAA, Hartley JA, Nixon HC, Evans H, Wadhwa RR, Kershaw C, Ince PG, Shaw PJ. Mutations in vapb are not associated with sporadic amyotrophic lateral sclerosis. Neurology 68: 1951-1953 (2007)

Dewil M, Kiraly D, Sciot R, Shaw PJ, Ince PG, Robberecht WD, Van Den Bosch, L. VEGF counteracts the loss of activated Akt preceding motoneuron degeneration in ALS. Neurpathol App Neurobiol 33: 499-509 (2007)

Simpson JE, Ince P G, Higham CE, Gelsthorpe CH, Fernando MS, Matthews F, Forster G, O´Brien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Stoeber K, Williams GH, Lewis CE, Wharton SB, on behalf of the MRC Cognitive Function and Ageing Neuropathology Study Group. Microglial activation characterises white matter lesions and the non-lesional white matter. Neuropathol App Neurobiol 33; 670–683 (2007)

Kasperavičiūtė D, Weale M, Shianna KV, Banks GT, Simpson CL, Hansen VK, Turner MR, Al-Chalabi A, Pall HS, Goodall EF, Morrison KE, Orrell RW, Beck M, Jablonka S, Sendtner M, Brockington A, Ince PG, Hartley J, Nixon H, Shaw PJ, Schiavo G, Wood NW, Goldstein DB, Fisher EMC. Large-scale pathways based association study in amyotrophic lateral sclerosis Brain 130: 2292 – 2301 (2007)

Mackenzie IRA, Bigio EH, Ince PG, Geser F, Neumann M, Cairns NJ, Kwong LK, Forman MS, Ravits J, Shaw PJ, Stewart H, Eisen A, McClusky L, Kretzschmar HA, Monoranu CM, Highley R, Kirby J, Siddique T, Lee VM-Y, Trojanowski JQ. Pathological TDP-43 distinguishes sporadic ALS from ALS with SOD-1 mutations. Ann Neurol 61; 427-34 (2007)

Cairns NJ, Bigio EH, MacKenzie IRA, Neumann M, Lee VM-Y, Hatanpaa KJ, Whitee CL III, Schneider JA, Grinberg LT, Halliday G, Duyckaerts C, Lowe JS, Holm IE, Tolnay M, Okamoto K, Yokoo H, Murayama S, Woulfe J, Munoz DG, Dickson DW, Ince PG, Trojanowski JQ, Mann DMA. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114: 5-22 (2007)