Professor Seth Love

Photo of Professor Seth Love

Professor Seth Love

Department of Neuropathology, Frenchay Hospital, Bristol
BS16 1LE
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seth.love@bristol.ac.uk

Fax Number (0117) 34 03760
Telephone Number (0117) 340 2386
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Organisations

School of Clinical Sciences

Neuropathology, NBT

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Dementia Research

Research overview

Over the past ten years much of Professor Love's research has focused on the pathogenesis of nerve cell damage and death in neurological disease - Alzheimer's disease in particular. Together with Dr Patrick Kehoe, he leads the Dementia Research Group, a part of the Institute of Clinical Neurosciences. He is Head of Section of Clinical Neurosciences in the School of Clinical Sciences, Faculty of Medicine and Dentistry.

Most of Seth's current research is in Alzheimer's disease, Lewy body dementia and vascular dementia, and concerns the pathogenesis and consequences of reduced cerebral blood flow in the different forms of dementia, the metabolism and clearance of Aβ and α-synuclein, and the molecular interrelationships between Alzheimer's disease, Lewy body diseases and vascular dementia. His research is currently supported by the Medical Research Council, Alzheimer's Research UK, the Alzheimer's Society, the British Heart Foundation and BRACE (Bristol Research into Alzheimer's and Care of the Elderly).

Key words

Apolipoprotein E, amyloid, ischaemia, perineuronal net, extracellular matrix

Key findings

Recent key findings of the Dementia Research Group include the following:

 

  • The expression of endothelin-converting enzyme-2 (which catalyses the production of the potent vasoconstrictor endothelin-1) is up-regulated by Aβ and increased in Alzheimer’s disease.
  • In Alzheimer's disease phosphorylated tau binds and sequesters pSmad3 translocation, an intracellular mediator of TGFβ signal transduction, potentially interfering with the transcription of a range of TGFβ target genes.
  • Picalm, a protein essential for clathrin-mediated endocytosis and the product of a gene recently shown in recent genome-wide association studies to be linked to Alzheimer's disease, is abundantly expressed by cerebrovascular endothelial cells, where it may be involved in the transport of Aβ across vessel walls and into the bloodstream.
  • The activity of Aβ-degrading enzymes neprilysin, insulin-degrading enzyme and angiotensin-converting enzyme, and the activity of BACE-1 (the rate-limiting enzyme in Aβ production) are all elevated in the brain in Alzheimer’s disease and increase with normal ageing.
  • In contrast to insoluble Aβ, the concentration of which increases with age and is significantly higher in the brain in Alzheimer’s disease than age-matched controls, levels of total soluble and oligomeric Aβ normally decline with age and are significantly higher in younger adults than older adults with or without Alzheimer’s disease. 

Diseases related to this field of research

Alzheimer's disease, vascular dementia, dementia with Lewy bodies, cerebral amyloid angiopathy

Processes and functions relevant to this work

Mechanisms of neurodegeneration, oxidative stress, vascular function, Aβ clearance and degradation

Research group

Emma Ashby, Shabnam Baig, Rachel Barber, Rachel Barker, Neil Barua, Katy Chalmers, Louisa Cockbill, Doris Culpan, Tom Fraser, Sam Lamprey, Joanna McTiernan, Scott Miners, Jennifer Palmer, Laura Palmer, Lindsey Sinclair, Marta Swirski, Hannah Tayler, Taya Thomas, Wan Wan Ruzali

Techniques in routine use

Microscopy (including quantitative immunohistochemical techniques and confocal scanning laser microscopy), protein biochemistry, enzyme assays, cell culture, gene expression studies

Collaborations

Dr Elizabeth Coulthard (Dementia Neurology, BRACE Centre, School of Clinical Sciences) Professor Steven Gill, Dr Alison Bienemann, Mr Edward White (Functional Neurosurgery, School of Clinical Sciences) Professor Julian Paton (Cardiovascular studies, School of Physiology and Pharmacology) Professor Scolding, Dr Alastair Wilkins and Dr Alan Whone (Academic Neurology, School of Clinical Sciences) Professors Andrew Whitelaw and Marianne Thoresen (Neonatal Neurology, School of Clinical Sciences)

Teaching

Teaching of neuropathology to Y2 and Y5 medical students; regular contributor to local, national and international neuroscience courses and seminars; member of the Pathology Education Program review panel of the International Network for Cancer Treatment and Research

Public engagement

Neuropathology of dementia, particularly Alzheimer's disease, vascular dementia and dementia with Lewy bodies, cerebral amyloid angiopathy




Latest publications

  1. Barker, R, Ashby, EL, Wellington, D, Barrow, VM, Palmer, JC, Kehoe, PG, Esiri, MM & Love, S 2014, ‘Pathophysiology of white matter perfusion in Alzheimer's disease and vascular dementia’. Brain.
  2. Miners, S, Moulding, H, Silva, Rd & Love, S 2014, ‘Reduced vascular endothelial growth factor and capillary density in the occipital cortex in dementia with Lewy bodies’. Brain Pathology.
  3. Miners, JS, Jones, R & Love, S 2014, ‘Differential Changes in Aβ42 and Aβ40 with Age’. J Alzheimers Dis.
  4. Barker, RM, Wellington, D, Esiri, M & Love, S 2013, ‘Assessing white matter ischemic damage in dementia patients by measurement of myelin proteins’. Journal of Cerebral Blood Flow and Metabolism, vol 33., pp. 1050-1057
  5. Ruzali, WAW, Kehoe, PG & Love, S 2013, ‘Influence of LRP-1 and Apolipoprotein E on Amyloid-β Uptake and Toxicity to Cerebrovascular Smooth Muscle Cells’. Journal of Alzheimer's Disease, vol 33., pp. 95-110
  6. Whitehouse, IJ, Miners, JS, Glennon, EBC, Kehoe, PG, Love, S, Kellett, KAB & Hooper, NM 2013, ‘Prion protein is decreased in Alzheimer's brain and inversely correlates with BACE1 activity, amyloid-β levels and Braak stage’. PloS one, vol 8., pp. e59554
  7. Glennon, EBC, Whitehouse, IJ, Miners, JS, Kehoe, PG, Love, S, Kellett, KAB & Hooper, NM 2013, ‘BIN1 Is Decreased in Sporadic but Not Familial Alzheimer's Disease or in Aging’. PloS one, vol 8., pp. e78806
  8. Lambert, J-C, Ibrahim-Verbaas, CA, Harold, D, Naj, AC, Sims, R, Bellenguez, C, Jun, G, Destefano, AL, Bis, JC, Beecham, GW, Grenier-Boley, B, Russo, G, Thornton-Wells, TA, Jones, N, Smith, AV, Chouraki, V, Thomas, C, Ikram, MA, Zelenika, D, Vardarajan, BN, Kamatani, Y, Lin, C-F, Gerrish, A, Schmidt, H, Kunkle, B, Dunstan, ML, Ruiz, A, Bihoreau, M-T, Choi, S-H, Reitz, C, Pasquier, F, Hollingworth, P, Ramirez, A, Hanon, O, Fitzpatrick, AL, Buxbaum, JD, Campion, D, Crane, PK, Baldwin, C, Becker, T, Gudnason, V, Cruchaga, C, Craig, D, Amin, N, Berr, C, Lopez, OL, De Jager, PL, Deramecourt, V, Johnston, JA, Evans, D, Lovestone, S, Letenneur, L, Morón, FJ, Rubinsztein, DC, Eiriksdottir, G, Sleegers, K, Goate, AM, Fiévet, N, Huentelman, MJ, Gill, M, Brown, K, Kamboh, MI, Keller, L, Barberger-Gateau, P, McGuinness, B, Larson, EB, Green, R, Myers, AJ, Dufouil, C, Todd, S, Wallon, D, Love, S, Rogaeva, E, Gallacher, J, St George-Hyslop, P, Clarimon, J, Lleo, A, Bayer, A, Tsuang, DW, Yu, L, Tsolaki, M, Bossù, P, Spalletta, G, Proitsi, P, Collinge, J, Sorbi, S, Sanchez-Garcia, F, Fox, NC, Hardy, J, Naranjo, MCD, Bosco, P, Clarke, R, Brayne, C, Galimberti, D, Mancuso, M, Matthews, F, Moebus, S, Mecocci, P, Zompo, MD, Maier, W, Hampel, H, Pilotto, A, Bullido, M, Panza, F, Caffarra, P, Nacmias, B, Gilbert, JR, Mayhaus, M, Lannfelt, L, Hakonarson, H, Pichler, S, Carrasquillo, MM, Ingelsson, M, Beekly, D, Alvarez, V, Zou, F, Valladares, O, Younkin, SG, Coto, E, Hamilton-Nelson, KL, Gu, W, Razquin, C, Pastor, P, Mateo, I, Owen, MJ, Faber, KM, Jonsson, PV, Combarros, O, O'Donovan, MC, Cantwell, LB, Soininen, H, Blacker, D, Mead, S, Mosley, TH, Bennett, DA, Harris, TB, Fratiglioni, L, Holmes, C, Bruijn, RFAGd, Passmore, P, Montine, TJ, Bettens, K, Rotter, JI, Brice, A, Morgan, K, Foroud, TM, Kukull, WA, Hannequin, D, Powell, JF, Nalls, MA, Ritchie, K, Lunetta, KL, Kauwe, JSK, Boerwinkle, E, Riemenschneider, M, Boada, M, Hiltunen, M, Martin, ER, Schmidt, R, Rujescu, D, Wang, L-S, Dartigues, J-F, Mayeux, R, Tzourio, C, Hofman, A, Nöthen, MM, Graff, C, Psaty, BM, Jones, L, Haines, JL, Holmans, PA, Lathrop, M, Pericak-Vance, MA, Launer, LJ, Farrer, LA, Duijn, CMv, Van Broeckhoven, C, Moskvina, V, Seshadri, S, Williams, J, Schellenberg, GD, Amouyel, P & 2013, ‘Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease’. NAT GENET.
  9. Gray, E, Rice, C, Nightingale, H, Ginty, M, Hares, K, Kemp, K, Cohen, N, Love, S, Scolding, N & Wilkins, A 2013, ‘Accumulation of cortical hyperphosphorylated neurofilaments as a marker of neurodegeneration in multiple sclerosis’. Multiple sclerosis (Houndmills, Basingstoke, England), vol 19., pp. 153-161
  10. Conway, ME, El Hindy, M, Hezwani, M, Hull, J, Corry, D, Mansbridge, A, Hassler, M, Patel, VB, Kehoe, PG, Love, S, Harris, M, Forshaw, T, Lee, CS, El Amraoui, F & Wilson, A 2013, ‘THE BRANCHED-CHAIN AMINOTRANSFERASE PROTEINS: NOVEL REDOX CHAPERONES FOR PROTEIN DISULFIDE ISOMERASE- IMPLICATIONS IN ALZHEIMER'S DISEASE’. Antioxidants & redox signaling.

Full publications list in the University of Bristol publications system

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