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Medicine
Phone:
(023) 8120 6634
Email:
J.Nicoll@soton.ac.uk

Professor James Nicoll BSc, MBChB, MD, FRCPath

Professor of Neuropathology

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Professor James Nicoll is Professor of Neuropathology within Medicine at the University of Southampton.

 Prof Nicoll was appointed to the Chair of Neuropathology in 2001. Having graduated in Medicine from the University of Bristol, he trained in Pathology in Oxford and Cardiff and returned to Bristol to undertake specialist training in Neuropathology (1987-1992). He completed his MD in Bristol investigating the role of herpes simplex virus in neurological disease using molecular tools. He then held a clinical academic post in Neuropathology at the Institute of Neurological Sciences/University of Glasgow. While in Glasgow he developed interests in the parallels between the response of the brain to acute injury, for example due to trauma or stroke, and Alzheimer's disease; specifically that they share common cellular reactions, upregulation of similar proteins and possibly share genetic influences.

Prof Nicoll has been Professor of Neuropathology and Honorary Consultant Neuropathologist in Southampton since 2001. He shares responsibility for providing the clinical diagnostic neuropathology service to the Wessex Region (a population of approximately 3 million). He is involved in associated undergraduate and postgraduate teaching and training has co-authored an introductory textbook on Neuropathology (Adams & Graham's Introduction to Neuropathology. 3rd Edition. Graham DI, Nicoll JAR & Bone I. Published by Hodder Arnold, London, 2006. ISBN 0 340 81197 9). He is a Fellow of the Royal College of Pathologists and a member of the British Neuropathological Society. He participates in the Royal College of Pathologists Continuing Professional Development Scheme and the UK Neuropathology External Quality Assurance Scheme. He also has experience in medicolegal aspects of Neuropathology.

In Southampton Prof Nicoll has continued his research interests in neuroinflammation, neurodegeneration and cerebrovascular disease. His work closely links diagnostic neuropathology and neuroscience research. He and his colleagues were the first in the world to describe and characterise the effects on the brain of immunisation against Aβ, being used as potential therapy in Alzheimer's disease.

Qualifications

BSc, Physiology, University of Bristol (1981)
MB ChB, University of Bristol (1984)
MRCPath, Neuropathology (1990)
MD, University of Bristol (1993)
FRCPath, Neuropathology (1999)

Appointments held

Senior Registrar, Department of Neuropathology Frenchay Hospital, Bristol. 1987-1992

Senior Lecturer/Reader/Professor and Honorary Consultant in Neuropathology, University of Glasgow, Institute of Neurological Sciences, Glasgow. 1992-2001

Professor of Neuropathology, University of Southampton and Hon Consultant in Neuropathology, Southampton University Hospitals NHS Trust. 2001-present

Research

Responsibilities

Publications

Teaching

Contact

Research interests

 My major research interests are in fields of neurodegeneration, brain injury, cerebrovascular disease and the potential for regeneration in the brain. I am particularly interested in underlying disease mechanisms and how genetic variation influences disease processes in the brain.

Current projects:

i) The effects of Aβ immunisation on the brain in Alzheimer's disease

After promising experimental studies, the first human trial of Aβ immunisation in Alzheimer's disease was undertaken by Elan Pharmaceuticals and recruited patients from across southern Britain, including Southampton. As a consequence we had the opportunity to be the first to observe, and attempt to understand, the effects of Aβ immunisation on the brain in Alzheimer's disease (Nicoll et al, Nature Medicine, 2003, 9, 448; Nicoll et al. JNEN, 2006, 65, 1040). The findings are remarkable in that this approach can modify the underlying neurodegenerative process, specifically by removing the plaques from the cerebral cortex. In collaboration with our colleagues in other centres across southern Britain we have performed a long term clinical and neuropathological follow-up of patients who were recruited to this study (Holmes et al, Lancet, 2008, 372, 216). These studies confirm that removal of Aβ plaques can occur following Aβ immunisation, sometimes almost completely, but that this does not seem to be sufficient to halt the progressive neurodegeneration. Current work attempts to understand the complex sequence of changes in the Alzheimer brain that is provoked by immunotherapy which includes alterations in the associated tau pathology (Boche et al, Acta Neuropathol, 2010, 120, 13), the cerebral vasculature (Boche et al, Brain, 2008, 131, 3299), the microglia (Zotova et al Neuropath Appl Neurobiol, 2011, 37, 513 & Brain, 2013, 136, 2677) and soluble Aβ (Maarouf et al Mol Neurodegeneration, 2010, 2, 39). Understanding the pathophysiological responses (Boche et al, Acta Neuropathol. 2010, 120, 369) may help to guide and understand the results from the many current clinical trials of Aβ immunotherapy for this common, distressing and costly disease. This work is funded by Alzheimer's Research UK.

ii) Neuroinflammation in Alzheimer's disease

The hypothesis being explored in this study is that the Aβ protein which accumulates as the plaques in Alzheimer's disease causes cognitive dysfunction indirectly by provoking an inflammatory reaction, activating microglia, which in turn damages the neurons (Perry et al, Nature Reviews Neurology, 2010, 6, 193; Boche & Nicoll, Neuropathol Appl Neurobiol, 2013, 39, 3). This follows previous work suggesting that specific polymorphisms in the genes encoding the cytokine IL-1 are over-represented in Alzheimer's disease (Nicoll et al, Ann Neurol, 2000, 47, 365-8) and more recent GWAS data implicating inflammatory processes. Current projects include a collaboration with the Cognitive Function in Ageing Study (Ince, Sheffield and Brayne, Cambridge), funded by the MRC, and assessment of the role of systemic inflammation on microglial activation, funded by Alzheimer's Research UK. Mediation of neurodegeneration in Alzheimer's disease by microglial activation has considerable implications in terms of in vivo imaging and therapy.

iii) The role of vascular changes in ageing and Alzheimer's disease

Changes in the blood vessels are a ubiquitous feature of the ageing brain and play an important, but poorly understood, role in cognitive dysfunction. The Weller perivascular drainage hypothesis (Weller et al, Acta Neuropathologica, 2009, 118, 87) states that extracellular fluid in the brain drains out of the brain, analogous to the lymphatics in other organs, along the walls of blood vessels. Impairment of drainage due to vessel ageing causes accumulation of Aβ in the walls of cerebral vessels (cerebral amyloid angiopathy) and may have detrimental effects on brain homeostasis, contributing to cognitive dysfunction. I collaborate with colleagues (Carare and Hawkes) who are pursuing this concept in human and animal studies (Carare et al, Neuropath Appl Neurobiol, 2008, 34, 13; Hawkes et al, Acta Neuropathologica, 2011, 121, 431; Hawkes et al, 2012, PloS One, 7, e41636).

iv) Neuroinflammation in traumatic brain injury

There is a microglial response in the brain after head injury which may persist for a prolonged period (Smith et al Neuropathol Appl Neurobiol 2013, 39, 654) and affect neuronal function. We have found evidence that cytokine gene polymorphisms, notably TNFα, influence clinical outcome (Waters et al, J Neurotrauma, 30, 1710). Manipulating the neuroinflammatory response after traumatic brain injury may be a therapeutic option.

v) The role of APOE in neurological disease

APOE is important in transporting cholesterol and lipids to neurons for maintenance and repair and in accumulation of Aβ in the brain. The APOE gene polymorphism is the major genetic risk factor for Alzheimer's disease, correlating strongly with the neuropathological features (Nicoll et al, Neuropath Appl Neurobiol, 2011, 37, 285); plays a role in outcome from traumatic brain injury (Nicoll et al Nature Medicine, 1995, 1, 135; Teasdale et al, 1997, Lancet, 350, 1069; Teasdale et al, Brain 2005, 128, 2556); and is a risk factor for stroke due to CAA-related haemorrhage (Nicoll et al, Ann Neurol, 1997, 41, 716).

vi) Brain Archive Information Network (BRAIN UK)

BRAIN UK (http://www.som.soton.ac.uk/research/sites/brainuk/) is a virtual Brain Bank which facilitates the use for research of brain tissue stored in the archives of Neuropathology departments throughout the UK. This project is an extended collaborative venture with many colleagues, supported by the British Neuropathological Society and funded by the MRC.

Academic unit(s)

Clinical and Experimental Sciences Academic Units

Affiliate academic unit(s)

Clinical Neuroscience Research group

 Postgraduate student supervision

2 PhD, 3 MD, 5 MSc completed
2 PhD current
Clinical academic trainees in Neurosurgery

National and International responsibilities

Director, UK Brain Archive Information Network (BRAIN UK)(2008 on)
Scientific Advisory Board, Alzheimer's Research UK (2010 on)
Examiner in Neuropathology, Royal College of Pathologists (2001 on)
Chair of Academic Committee, British Neuropathological Society (2012 on)
Editorial Board, Brain Pathology (2000 on)
Editorial Board, Neuropathology & Applied Neurobiology (2013 on)
Councillor, International Society of Neuropathology (2013 on)
London Neurodegenerative Diseases Brain Bank Tissue request committee (2013 on)
Consultant/advisor to several major pharmaceutical companies relating to Alzheimer immunisation programmes
>80 external invited presentations

Article(s)

Book Section(s)

Conference(s)

 BM4/5
Semester 1 Pathology tutorials
Semester 1 Introduction to Pathology of the Nervous System
Semester 3 Neuropathology tutorials
Semester 3 Dementia symposium

Neuropathology seminars for postgraduate clinical trainees in Pathology and on occasions Neurology, Neurosurgery, Neuro-oncology and Psychiatry.

Examinations
BM Intermediate examination examiner (written papers, OSCEs and vivas)
BM Final OSCE examiner
PhD and transfer thesis examiner (University of Southampton and external)
External examiner, Imperial College, Neuroscience & Mental Health BSc (2013 on)

Professor James Nicoll
Faculty of Medicine University of Southampton Southampton General Hospital Mailpoint 813 South Academic Block Tremona Road Southampton SO16 6YD

Room Number: SGH/LE63/MP813

Telephone: (023) 8120 6634
Email: J.Nicoll@soton.ac.uk

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