University of Southampton, School of Medicine

Faculty:   Faculty of Medicine and Health and Life Sciences
Department:   School of Medicine
Division:   Clinical Neurosciences

Contacts information

Email:  row@soton.ac.uk

Phone:  N/A

Address:
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Staff Photograph

Microvasculature changes and cerebral amyloid angiopathy in Alzheimer''s disease and their potential impact on therapy. (Acta Neuropathological 118:87-102)
Roy O. Weller, Delphine Boche, James A.R. Nicoll, (2009-07)

Lymphatic drainage of the brain and the pathophysiology of neurological disease (Acta Neuropathologica 117:1-14)
Roy O. Weller, Effie. Djuanda, Hong-Yeen Yow, Roxana O. Carare, (2009-01)

Failure of elimination of amyloid-beta from the brain in Alzheimer''s disease (Progress in Neurology and Psychiatry 12:6-10)
Prasanna de Silva, Roxana O. Carare, Roy O. Weller, (2008-05)

Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology (Neuropathology & Applied Neurobiology 34:131-144)
R.O. Carare, M. Bernardes-Silva, T.A. Newman, A.M. Page, J.A.R. Nicoll, V.H. Perry, R.O. Weller, (2008-04)

Perivascular drainage of amyloid-β peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer''s disease. [In: Symposium on the Neuropathology of Alzheimer''s Disease] (Brain Pathology 18:253-266)
Roy O. Weller, Malavika Subash, Stephen D. Preston, Ingrid Mazanti, Roxana O. Carare, (2008-03-19)

Immune complexes formed in the brain disrupt the perivascular drainage of solutes and interstitial fluid: significance for immunotherapy in Alzheimer''s disease (Neuropathology and Applied Neurobiology 34:p.2)
R.O. Carare, J. Teeling, V.H. Perry, J.A.R. Nicoll, R.O. Weller, (2008-01-04)

Biological consequences of immune complexes formation in the brain; implications for immunotherapy to treat Alzheimer''s disease (Defect and Diffusion Forum 34:1-1)
J.L. Teeling, R.O. Carare, J.A.R. Nicoll, R.O. Weller, V.H. Perry, (2008-01-01)

Biological consequences of immune complexes formation in the brain; implications for immunotherapy to treat Alzheimer''s disease (Neuropathology and Applied Neurobiology 34:1-1)
J.L. Teeling, R.O. Carare, J.A.R. Nicoll, R.O. Weller, V.H. Perry, (2008-01)

Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology (Neuropathology and Applied Neurobiology 34:131-144)
R. O. Carare, M. Bernardes-Silva, T. A. Newman, A. M. Page, J. A. Nicoll, V. H. Perry, R. O. Weller, (2008)

Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology (Neuropathology and Applied Neurobiology 34:131-144)
RO Carare, M Bernardes-Silva, TA Newman, AM Page, JAR Nicoll, VH Perry, RO Weller, (2008)

Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer''s disease (Brain Pathology 18:253-266)
R.O. Weller, M. Subash, S.D. Preston, I. Mazanti, R.O. Carare, (2008)

Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer''s disease (Brain Pathology 18:253-266)
Roy O. Weller, Malavika Subash, Stephen D. Preston, Ingrid Mazanti, Roxana O. Carare, (2008)

The phagocytic capacity of neurones (European Journal of Neuroscience 25:2947-2955)
Samantha Bowen, Davidson D. Ateh, Katrin Deinhardt, Margaret M. Bird, Karen M. Price, Cathy S. Baker, Joanna C. Robson, Michael Swash, Wassim Shamsuddin, Shalini Kawar, Tariq El-Tawil, Jesper Roos, Andrew Hoyle, Carole D. Nickols, Charles H. Knowles, Anthony H. Pullen, Philip J. Luthert, Roy O. Weller, Majid Hafezparast, Robin J.M. Franklin, Tamas Revesz, Rosalind H.M. King, Otto Berninghausen, Elizabeth M.C. Fisher, Giampietro Schiavo, Joanne E. Martin, (2007)

Cerebrovascular disease impedes the perivascular elimination of amyloid-beta from the brain in Alzheimer''s disease (Brain Pathology 16:p.S79)
RO. Weller, R. Carare-Nnadi, HY. Yow, D. Boche, I. Mazanti, LR. Bridges, VH. Perry, JA. Nicoll, (2006-09)

Letters to the editor: an unusual familial oculopharyngeal syndrome (European Journal of Neurology 13:549-550)
S.A. Cooper, M.E. Hill, R.O. Weller, S.R. Hammans, (2006-05)

Connections between perivascular interstitial fluid drainage pathways in the brain: Significance for Alzheimer''s disease and neuroimmunology (Neuropathology and Applied Neurobiology 32:p.223)
R. Carare-Nnadi, M. Bernardes-Silva, M. Subash, V.H. Perry, R.O. Weller, (2006-04-01)

Effects of Aβ immunotherapy on cerebral amyloid angiopathy in Alzheimer’s disease (Neuropathology and Applied Neurobiology 32:223-224)
D. Boche, E. Barton, J. Neal, I. Ferrer, D. Wilkinson, A. Bayer, C. Holmes, RO. Weller, JAR. Nicoll, (2006-04)

Connections between perivascular interstitial fluid drainage pathways in the brain: significance for Alzheimer''s disease and neuroimmunology (Neuropathology and Applied Neurobiology 32:p.223)
R. Carare-Nnadi, M. Bernardes-Silva, M. Subash, V.H. Perry, R.O. Weller, (2006-03-13)

Mechanisms to explain the reverse perivascular transport of solutes out of the brain (Journal of Theoretical Biology 238:962-974)
D. Schley, R. Carare-Nnadi, C.P. Please, V.H. Perry, R.O. Weller, (2006-02-21)

Mechanisms to explain the reverse perivascular transport of solutes out of the brain (Journal of Theoretical Biology 238:962-974)
D. Schley, R. Carare-Nnadi, C.P. Please, V.H. Perry, R.O. Weller, (2006-02-01)

Mechanisms to explain the reverse perivascular transport of solutes out of the brain (Journal of Theoretical Biology 238:962-974)
D. Schley, R. Carare-Nnadi, C.P. Please, V.H. Perry, R.O. Weller, (2006-02)

Immunotherapy for Alzheimer''s disease and other dementias (Clinical Neuropharmacology 29:22-27)
D. Boche, JAR. Nicoll, RO. Weller, (2006-01)

Neuropathology in Europe: an overview (Clinical Neuropathology 25:7-13)
J. Mikol, R. Weller, (2006-01)

Mechanisms to explain the reverse perivascular transport of solutes out of the brain (Journal of Theoretical Biology 238:962-974)
D. Schley, R. Carare-Nnadi, C.P. Please, V.H. Perry, R.O. Weller, (2006)

Comment [In Primary CNS lymphoma in immunocompetent patients from 1989 to 2001: a retrospective analysis of 164 cases uniformly diagnosed by stereotactic biopsy p.838] (Acta Neurochirurgica 148:831-838)
R.O. Weller, (2006)

Immunotherapy for Alzheimer''s disease and other dementias (Current Opinion in Neurology 18:720-725)
D. Boche, JAR. Nicoll, RO. Weller, (2005-12)

Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease (Annals of Neurology 57:310-326)
Rong Li, Anne B. Johnson, Gajja Salomons, James E. Goldman, Sakkubai Naidu, Roy Quinlan, Bruce Cree, Stephanie Z. Ruyle, Brenda Banwell, Marc D''Hooghe, Joseph R. Siebert, Cristin M. Rolf, Helen Cox, Alyssa Reddy, Luis Gonzalez Gutierrez-Solana, Amanda Collins, Roy O. Weller, Albee Messing, Marjo S. van der Knaap, Michael Brenner, (2005-03)

Perivascular pathways for the clearance of interstitial fluid from the brain and the pathology of Alzheimer''s disease (Neuropathology and Applied Neurobiology 31:210-245)
R. Carare-Nnadi, M. Bernardes-Silva, M. Subash, V.H. Perry, R.O. Weller, (2005)

Giant tumefactive perivascular spaces (American Journal of Neuroradiology 26:298-305)
Karen L. Salzman, Anne G. Osborn, Paul House, J. Randy Jinkins, Adam Ditchfield, James A. Cooper, Roy O. Weller, (2005)

Cytokine-induced enhancement of autoimmune inflammation in the brain and spinal cord: implications for multiple sclerosis (Neuropathology and Applied Neurobiology 30:374-384)
D. Sun, T.A. Newman, V.H. Perry, R.O. Weller, (2004-08-01)

Genetic and expression profiles of cerebellar liponeurocytomas (Brain Pathology 14:281-289)
Sonia Horstmann, Arie Perry, Guido Reifenberger, Felice Giangaspero, Herve Huang, Akira Hara, Jun Masuoka, Nikolai G. Rainov, Markus Bergmann, Frank L. Heppner, Sebastian Brandner, Leila Chimelli, Nadia Montagna, Thad Jackson, Daron G. Davis, William R. Markesbery, David W. Ellison, Roy O. Weller, Gian L. Taddei, Renato Conti, Marc R. Del Bigio, Ricardo Gonzalez-Campora, V.V. Radhakrishnan, Figen Soylemzoglu, Emmanuelle Uro-Coste, Jiang Qian, Paul Kleihues, Hiroko Ohgaki, (2004-07)

Reply to "Specificity of mechanisms for plaque removal after abeta immunotherapy for alzheimer disease (Nature medicine 10:118-119)
James A. Nicoll, David E. Wilkinson, Clive Holmes, Phil Steart, Hannah Markham, Roy O. Weller, (2004-02)

Different meningitis-causing bacteria induce distinct inflammatory responses on interaction with cells of the human meninges (Cellular Microbiology 6:555-567)
Mark I. Fowler, Roy O. Weller, John E. Heckels, Myron Christodoulides, (2004)

Traffic of antigen presenting cells to and from the brain (Neuroimmunology 154:1-230)
T. Newman, R. Carare-Nnadi, M. Bernardes-Silva, R. Weller, V. H. Perry, (2004)

Traffic of antigen presenting cells to and from the brain (Neuroimmunology 154:p.15)
T. Newman, R. Carare-Nnadi, M. Bernardes-Silva, R. Weller, V.H. Perry, (2004)

Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer''s disease. Pro-CAA position statement (Neurobiology of Aging 25:589-597)
J.A. Nicoll, M. Yamada, J. Frackowiak, B. Mazur-Kolecka, R.O. Weller, (2004)

Development of vigabatrin-induced lesions in the rat brain studied by magnetic resonance imaging, histology and immunocytochemistry (Synapse 53:36-43)
N.E. Preece, J. Houseman, M.D. King, R.O. Weller, S.R. Williams, (2004)

Neuropathological assessment of artemether-treated severe malaria (The Lancet 362:295-296)
T.T. T. G. Hien, N.T. Mai, N.H. Phu, D. Bethell, W.F. Blakemore, J.B. Cavanagh, A. Dayan, I. Medana, R.O. Weller, N.P. Day, N.J. White, (2003)

A new role for astrocytes: β-amyloid homeostasis and degradation (Trends in Molecular Medicine 9:281-282)
James A.R. Nicoll, Roy O. Weller, (2003)

Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report (Nature Medicine 9:448-452)
James A.R. Nicoll, David Wilkinson, Clive Holmes, Phil Steart, Hannah Markham, Roy O. Weller, (2003)

Capillary and arterial cerebral amyloid angiopathy in Alzheimer''s disease: defining the perivascular route for the elimination of amyloid β from the human brain (Neuropathology & Applied Neurobiology 29:106-117)
S.D. Preston, P.V. Steart, A. Wilkinson, J.A.R. Nicoll, R.O. Weller, (2003)

Cortical and leptomeningeal cerebrovascular amyloid and white matter pathology in Alzheimer''s disease (Molecular Medicine 9:112-122)
Alex E. Roher, Yu-Min Kuo, Chera Esh, Carmen Knebel, Nicole Weiss, Walter Kalback, Dean C. Luehrs, Jennifer L. Childress, Thomas G. Beach, Roy O. Weller, Tyler A. Kokjohn, (2003)

Cerebral amyloid angiopathy: pathogenesis and effects on the ageing and Alzheimer brain (Neurological Research 25:611-616)
R.O. Weller, J.A. Nicoll, (2003)

Molecular pathogenesis of subarachnoid haemorrhage (The International Journal of Biochemistry & Cell Biology 35:1341-1360)
Baiping Zhang, Kaare Fugleholm, Lorna B. Day, Shu Ye, Roy O. Weller, Ian N.M. Day, (2003)

Cerebrovascular disease is a major factor in the failure of elimination of Aβ from the aging human brain: implications for therapy of Alzheimer''s disease (Annals of the New York Academy of Sciences :162-168)
Roy O. Weller, Hong-Yeen Yow, Stephen D. Preston, Ingrid Mazanti, James A.R. Nicoll, (2002)

Meeting report. XlVth International Congress of Neuropathology, 3-6 September, 2000, Birmingham, United Kingdom (Brain Pathology 11:250-258)
R.O. Weller, (2001)

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Although now I have only a minimal involvement in Clinical Diagnostic Neuropathology, I am still involved in research as outlined below. I also direct a teaching course on Multiprofessional and Multidisciplinary Education in Pathology.

My major current research fields are in Neuroimmunology and Alzheimer's disease.

Role of lymphatic drainage of the brain in autoimmune disease of the CNS

Using experimental models of neuroimmunological disease, my colleagues and I investigated the interrelationships between the brain and the immune system. As the brain has no conventional lymphatics, we first worked on characterising the perivascular pathways by which antigens drain from the brain to regional lymph nodes and then showed that cervical lymph nodes play an essential role in T-cell mediated immunity in the brain. Furthermore, we have shown that the local effect of proinflammatory cytokines on the brain is enhanced in autoimmune disease. This work has direct relevance not only for Multiple Sclerosis.

Cerebrovascular disease and the pathogenesis of Alzheimer's disease

Failure of drainage of fluid and solutes from the brain is also relevant for the pathogenesis of Alzheimer's disease. Pathways for fluid and antigen drainage from the human brain are along capillary and artery walls. Our work suggests that as arteries age and develop cerebrovascular disease, the drainage pathways for the drainage of soluble Amyloid-ß (Aß) become blocked and Aß accumulates in vessel walls as cerbral amyloid angiopathy and in the brain in Alzheimer's disease.

Pathophysiology of Alzheimer's disease

Alzheimer's disease is the most common dementia in Britain bringing devastation to the many elderly sufferers and their carers. Pathologically, Alzheimer's disease is characterised by the accumulation of proteins within neurons (tau, ubiquitin, etc.) and by the deposition of soluble and insoluble amyloid-ß (Aß) peptides in the extracellular spaces of cerebral grey matter and in artery and capillary walls. Our major research focus has been to define the routes by which Aß is normally eliminated from the human brain and why elimination of Aß fails with age and Alzheimer's disease.

Using data derived from our experimental work, from transgenic mice and from immunohistochemical and ultrastructural studies of human brains, we defined interstitial fluid drainage pathways along capillary and artery walls that act as elimination pathways for Aß from the human brain. The question remained as to why elimination of Aß along these pathways fails with age and Alzheimer's disease. Through correlative studies of cerebral vascular disease and patterns of distribution of Aß in ageing brains, we have shown a relationship between cerebrovascular disease and the failure of clearance of Aß along perivascular routes.

Our working hypothesis is that pulsations within arteries normally drive the elimination of interstitial fluid and Aß from the brain, A reduction in the strength of arterial pulsations with loss of elasticity in atherosclerotic hardened arteries in older individuals may reduce the speed of elimination of Aß. Such slowing of drainage may induce the precipitation of Aß in its insoluble ß-pleated sheet form within the brain and vessel walls. This work raises the strong possibility that in addition to Apolipoprotein E genotype and mutations in the amyloid precursor protein gene, cerebrovascular disease and the arteriosclerosis that involves much of the cerebral circulation as people age may be counted as a major risk factor for Alzheimer's disease.

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