people

the driving force behind the cararegroup

The Carare Group consists of experts in anatomy and physiology, neuropathology, experimental neurosurgery, advanced imaging and immunohistochemistry.

The team regularly collaborates with clinicians and other universities both locally and internationally and has several well established European and American grant programs. The Carare Group also works closely with several Key industry partners including United Neurosciences, Biogen, Codiak Biosciences and Yumanity.

Professor Roxana Carare

PRINCIPAL INVESTIGATOR

Roxana Carare is a medically qualified Professor of Clinical Neuroanatomy and experimental neuropathology in the University of Southampton.

r.o.carare@soton.ac.uk

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Publications

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In silico exploration of amyloid-related imaging abnormalities in the gantenerumab open-label extension trials using a semi-mechanistic model. Aldea, R, Grimm, HP, Gieschke, R, Hofmann, C, Lott, D et al.. Alzheimers Dement (N Y). 2022;8 (1):e12306. doi: 10.1002/trc2.12306. PubMed PMID:35676943 PubMed Central PMC9169977.

Quantifying cerebrospinal fluid dynamics: A review of human neuroimaging contributions to CSF physiology and neurodegenerative disease. Mehta, NH, Suss, RA, Dyke, JP, Theise, ND, Chiang, GC et al.. Neurobiol Dis. 2022;170 :105776. doi: 10.1016/j.nbd.2022.105776. PubMed PMID:35643187 .

Decreased CSF clearance and increased brain amyloid in Alzheimer's disease. Li, Y, Rusinek, H, Butler, T, Glodzik, L, Pirraglia, E et al.. Fluids Barriers CNS. 2022;19 (1):21. doi: 10.1186/s12987-022-00318-y. PubMed PMID:35287702 PubMed Central PMC8919541.

Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment. Li, M, Kitamura, A, Beverley, J, Koudelka, J, Duncombe, J et al.. Front Aging Neurosci. 2021;13 :788519. doi: 10.3389/fnagi.2021.788519. PubMed PMID:35095472 PubMed Central PMC8793139.

The Brain-Nose Interface: A Potential Cerebrospinal Fluid Clearance Site in Humans. Mehta, NH, Sherbansky, J, Kamer, AR, Carare, RO, Butler, T et al.. Front Physiol. 2021;12 :769948. doi: 10.3389/fphys.2021.769948. PubMed PMID:35058794 PubMed Central PMC8764168.

TUBE Project: Transport-Derived Ultrafines and the Brain Effects. Martikainen, MV, Aakko-Saksa, P, van den Broek, L, Cassee, FR, Carare, RO et al.. Int J Environ Res Public Health. 2021;19 (1):. doi: 10.3390/ijerph19010311. PubMed PMID:35010571 PubMed Central PMC8751045.

Physiology and Clinical Relevance of Enlarged Perivascular Spaces in the Aging Brain. Bown, CW, Carare, RO, Schrag, MS, Jefferson, AL. Neurology. 2022;98 (3):107-117. doi: 10.1212/WNL.0000000000013077. PubMed PMID:34810243 PubMed Central PMC8792814.

Immunisation with UB-312 in the Thy1SNCA mouse prevents motor performance deficits and oligomeric α-synuclein accumulation in the brain and gut. Nimmo, JT, Smith, H, Wang, CY, Teeling, JL, Nicoll, JAR et al.. Acta Neuropathol. 2022;143 (1):55-73. doi: 10.1007/s00401-021-02381-5. PubMed PMID:34741635 PubMed Central PMC8732825.

Gadolinium enhancement of cranial nerves: Implications for interstitial fluid drainage from brainstem into cranial nerves in humans. Varatharaj, A, Carare, RO, Weller, RO, Gawne-Cain, M, Galea, I et al.. Proc Natl Acad Sci U S A. 2021;118 (45):. doi: 10.1073/pnas.2106331118. PubMed PMID:34728566 PubMed Central PMC8609323.

The α-dystrobrevins play a key role in maintaining the structure and function of the extracellular matrix-significance for protein elimination failure arteriopathies. Sharp, MM, Cassidy, J, Thornton, T, Lyles, J, Keable, A et al.. Acta Neuropathol Commun. 2021;9 (1):171. doi: 10.1186/s40478-021-01274-8. PubMed PMID:34674769 PubMed Central PMC8532274.

Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials. Nimmo, JT, Kelly, L, Verma, A, Carare, RO, Nicoll, JAR et al.. Front Neurosci. 2021;15 :733857. doi: 10.3389/fnins.2021.733857. PubMed PMID:34539340 PubMed Central PMC8441015.

Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective Longitudinal Cohort Study. Antolini, L, DiFrancesco, JC, Zedde, M, Basso, G, Arighi, A et al.. Neurology. 2021;97 (18):e1809-e1822. doi: 10.1212/WNL.0000000000012778. PubMed PMID:34531298 PubMed Central PMC8610623.

Taxifolin: A Potential Therapeutic Agent for Cerebral Amyloid Angiopathy. Saito, S, Tanaka, M, Satoh-Asahara, N, Carare, RO, Ihara, M et al.. Front Pharmacol. 2021;12 :643357. doi: 10.3389/fphar.2021.643357. PubMed PMID:33643053 PubMed Central PMC7907591.

Cerebral Vessels: An Overview of Anatomy, Physiology, and Role in the Drainage of Fluids and Solutes. Agarwal, N, Carare, RO. Front Neurol. 2020;11 :611485. doi: 10.3389/fneur.2020.611485. PubMed PMID:33519691 PubMed Central PMC7838613.

Loss of cholinergic innervation differentially affects eNOS-mediated blood flow, drainage of Aβ and cerebral amyloid angiopathy in the cortex and hippocampus of adult mice. Nizari, S, Wells, JA, Carare, RO, Romero, IA, Hawkes, CA et al.. Acta Neuropathol Commun. 2021;9 (1):12. doi: 10.1186/s40478-020-01108-z. PubMed PMID:33413694 PubMed Central PMC7791879.

Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy. Nimmo, JT, Verma, A, Dodart, JC, Wang, CY, Savistchenko, J et al.. Alzheimers Res Ther. 2020;12 (1):159. doi: 10.1186/s13195-020-00727-x. PubMed PMID:33256825 PubMed Central PMC7702704.

Cerebral Amyloid Angiopathy Presenting as Massive Subarachnoid Haemorrhage: A Case Study and Review of Literature. Saito, S, Ikeda, Y, Ando, D, Carare, RO, Ishibashi-Ueda, H et al.. Front Aging Neurosci. 2020;12 :538456. doi: 10.3389/fnagi.2020.538456. PubMed PMID:33240073 PubMed Central PMC7683384.

Editorial: Intramural Vascular Cells: Key Therapeutic Targets for Vascular Cognitive Impairment. Saito, S, McLaurin, J, Carare, RO. Front Aging Neurosci. 2020;12 :615780. doi: 10.3389/fnagi.2020.615780. PubMed PMID:33192495 PubMed Central PMC7662129.

Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds. Hosoki, S, Saito, S, Tonomura, S, Ishiyama, H, Yoshimoto, T et al.. Stroke. 2020;51 (12):3632-3639. doi: 10.1161/STROKEAHA.120.029607. PubMed PMID:33148146 PubMed Central PMC7678651.

Retinal imaging in Alzheimer's and neurodegenerative diseases. Snyder, PJ, Alber, J, Alt, C, Bain, LJ, Bouma, BE et al.. Alzheimers Dement. 2021;17 (1):103-111. doi: 10.1002/alz.12179. PubMed PMID:33090722 PubMed Central PMC8062064.

Vascular α1A Adrenergic Receptors as a Potential Therapeutic Target for IPAD in Alzheimer's Disease. Frost, M, Keable, A, Baseley, D, Sealy, A, Andreea Zbarcea, D et al.. Pharmaceuticals (Basel). 2020;13 (9):. doi: 10.3390/ph13090261. PubMed PMID:32971843 PubMed Central PMC7560129.

Peri-arterial pathways for clearance of α-Synuclein and tau from the brain: Implications for the pathogenesis of dementias and for immunotherapy. Nimmo, J, Johnston, DA, Dodart, JC, MacGregor-Sharp, MT, Weller, RO et al.. Alzheimers Dement (Amst). 2020;12 (1):e12070. doi: 10.1002/dad2.12070. PubMed PMID:32782922 PubMed Central PMC7409108.

Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA): Cerebrovascular disease and the failure of elimination of Amyloid-β from the brain and retina with age and Alzheimer's disease-Opportunities for Therapy. Carare, RO, Aldea, R, Agarwal, N, Bacskai, BJ, Bechman, I et al.. Alzheimers Dement (Amst). 2020;12 (1):e12053. doi: 10.1002/dad2.12053. PubMed PMID:32775596 PubMed Central PMC7396859.

Demonstrating a reduced capacity for removal of fluid from cerebral white matter and hypoxia in areas of white matter hyperintensity associated with age and dementia. MacGregor Sharp, M, Saito, S, Keable, A, Gatherer, M, Aldea, R et al.. Acta Neuropathol Commun. 2020;8 (1):131. doi: 10.1186/s40478-020-01009-1. PubMed PMID:32771063 PubMed Central PMC7414710.

Retinal Vascular Pathology in a Rat Model of Cerebral Small Vessel Disease. Scheifele, HM, Ulbrich, P, Garz, C, Carare, RO, Heinze, HJ et al.. Front Neurol. 2020;11 :533. doi: 10.3389/fneur.2020.00533. PubMed PMID:32695061 PubMed Central PMC7338761.

ApoE4 Astrocytes Secrete Basement Membranes Rich in Fibronectin and Poor in Laminin Compared to ApoE3 Astrocytes. Keable, A, O'Neill, R, MacGregor Sharp, M, Gatherer, M, Yuen, HM et al.. Int J Mol Sci. 2020;21 (12):. doi: 10.3390/ijms21124371. PubMed PMID:32575521 PubMed Central PMC7352194.

Neurofilaments: neurobiological foundations for biomarker applications. Gafson, AR, Barthélemy, NR, Bomont, P, Carare, RO, Durham, HD et al.. Brain. 2020;143 (7):1975-1998. doi: 10.1093/brain/awaa098. PubMed PMID:32408345 PubMed Central PMC7363489.

UK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: Questionnaire and workshop proceedings. McFall, A, Hietamies, TM, Bernard, A, Aimable, M, Allan, SM et al.. J Cereb Blood Flow Metab. 2020;40 (7):1402-1414. doi: 10.1177/0271678X20910552. PubMed PMID:32151228 PubMed Central PMC7307003.

Vital Functions Contribute to the Spread of Extracellular Fluids in the Brain: Comparison Between Life and Death. Piotrowska, A, Winter, K, Carare, RO, Bechmann, I. Front Aging Neurosci. 2020;12 :15. doi: 10.3389/fnagi.2020.00015. PubMed PMID:32116648 PubMed Central PMC7027336.

The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy. Owasil, R, O'Neill, R, Keable, A, Nimmo, J, MacGregor Sharp, M et al.. Int J Mol Sci. 2020;21 (4):. doi: 10.3390/ijms21041225. PubMed PMID:32059400 PubMed Central PMC7072949.

Vasomotion Drives Periarterial Drainage of Aβ from the Brain. Carare, RO, Aldea, R, Bulters, D, Alzetani, A, Birch, AA et al.. Neuron. 2020;105 (3):400-401. doi: 10.1016/j.neuron.2020.01.011. PubMed PMID:32027828 .

The Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain. Dewing, JM, Carare, RO, Lotery, AJ, Ratnayaka, JA. Cells. 2019;9 (1):. doi: 10.3390/cells9010039. PubMed PMID:31877820 PubMed Central PMC7017234.

Solving an Old Dogma: Is it an Arteriole or a Venule?. MacGregor Sharp, M, Criswell, TP, Dobson, H, Finucane, C, Verma, A et al.. Front Aging Neurosci. 2019;11 :289. doi: 10.3389/fnagi.2019.00289. PubMed PMID:31695607 PubMed Central PMC6817770.

Brain pharmacology of intrathecal antisense oligonucleotides revealed through multimodal imaging. Mazur, C, Powers, B, Zasadny, K, Sullivan, JM, Dimant, H et al.. JCI Insight. 2019;4 (20):. doi: 10.1172/jci.insight.129240. PubMed PMID:31619586 PubMed Central PMC6824309.

Invited Review: The spectrum of age-related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathies. Schreiber, S, Wilisch-Neumann, A, Schreiber, F, Assmann, A, Scheumann, V et al.. Neuropathol Appl Neurobiol. 2020;46 (3):219-239. doi: 10.1111/nan.12576. PubMed PMID:31386773 .

Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction. Hase, Y, Polvikoski, TM, Firbank, MJ, Craggs, LJL, Hawthorne, E et al.. Brain Pathol. 2020;30 (1):191-202. doi: 10.1111/bpa.12769. PubMed PMID:31357238 PubMed Central PMC8018165.

3D Reconstruction of the Neurovascular Unit Reveals Differential Loss of Cholinergic Innervation in the Cortex and Hippocampus of the Adult Mouse Brain. Nizari, S, Carare, RO, Romero, IA, Hawkes, CA. Front Aging Neurosci. 2019;11 :172. doi: 10.3389/fnagi.2019.00172. PubMed PMID:31333445 PubMed Central PMC6620643.

Dispersion in porous media in oscillatory flow between flat plates: applications to intrathecal, periarterial and paraarterial solute transport in the central nervous system. Keith Sharp, M, Carare, RO, Martin, BA. Fluids Barriers CNS. 2019;16 (1):13. doi: 10.1186/s12987-019-0132-y. PubMed PMID:31056079 PubMed Central PMC6512764.

Knockout of apolipoprotein A-I decreases parenchymal and vascular β-amyloid pathology in the Tg2576 mouse model of Alzheimer's disease. Contu, L, Carare, RO, Hawkes, CA. Neuropathol Appl Neurobiol. 2019;45 (7):698-714. doi: 10.1111/nan.12556. PubMed PMID:31002190 .

Cerebrovascular Smooth Muscle Cells as the Drivers of Intramural Periarterial Drainage of the Brain. Aldea, R, Weller, RO, Wilcock, DM, Carare, RO, Richardson, G et al.. Front Aging Neurosci. 2019;11 :1. doi: 10.3389/fnagi.2019.00001. PubMed PMID:30740048 PubMed Central PMC6357927.

Vascular dysfunction-The disregarded partner of Alzheimer's disease. Sweeney, MD, Montagne, A, Sagare, AP, Nation, DA, Schneider, LS et al.. Alzheimers Dement. 2019;15 (1):158-167. doi: 10.1016/j.jalz.2018.07.222. PubMed PMID:30642436 PubMed Central PMC6338083.

CSF Neurofilament Light Chain Levels in Primary Progressive MS: Signs of Axonal Neurodegeneration. Pawlitzki, M, Schreiber, S, Bittner, D, Kreipe, J, Leypoldt, F et al.. Front Neurol. 2018;9 :1037. doi: 10.3389/fneur.2018.01037. PubMed PMID:30631300 PubMed Central PMC6315185.

Military-related risk factors for dementia. Snyder, HM, Carare, RO, DeKosky, ST, de Leon, MJ, Dykxhoorn, D et al.. Alzheimers Dement. 2018;14 (12):1651-1662. doi: 10.1016/j.jalz.2018.08.011. PubMed PMID:30415806 PubMed Central PMC6281800.

A control mechanism for intra-mural peri-arterial drainage via astrocytes: How neuronal activity could improve waste clearance from the brain. Diem, AK, Carare, RO, Weller, RO, Bressloff, NW. PLoS One. 2018;13 (10):e0205276. doi: 10.1371/journal.pone.0205276. PubMed PMID:30286191 PubMed Central PMC6171921.

The association between hypertensive arteriopathy and cerebral amyloid angiopathy in spontaneously hypertensive stroke-prone rats. Jandke, S, Garz, C, Schwanke, D, Sendtner, M, Heinze, HJ et al.. Brain Pathol. 2018;28 (6):844-859. doi: 10.1111/bpa.12629. PubMed PMID:30062722 PubMed Central PMC8028507.

Convective influx/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways. Albargothy, NJ, Johnston, DA, MacGregor-Sharp, M, Weller, RO, Verma, A et al.. Acta Neuropathol. 2018;136 (1):139-152. doi: 10.1007/s00401-018-1862-7. PubMed PMID:29754206 PubMed Central PMC6015107.

Small vessels, dementia and chronic diseases - molecular mechanisms and pathophysiology. Horsburgh, K, Wardlaw, JM, van Agtmael, T, Allan, SM, Ashford, MLJ et al.. Clin Sci (Lond). 2018;132 (8):851-868. doi: 10.1042/CS20171620. PubMed PMID:29712883 PubMed Central PMC6700732.

The fine anatomy of the perivascular compartment in the human brain: relevance to dilated perivascular spaces in cerebral amyloid angiopathy. MacGregor Sharp, M, Bulters, D, Brandner, S, Holton, J, Verma, A et al.. Neuropathol Appl Neurobiol. 2019;45 (3):305-308. doi: 10.1111/nan.12480. PubMed PMID:29486067 .

The meninges as barriers and facilitators for the movement of fluid, cells and pathogens related to the rodent and human CNS. Weller, RO, Sharp, MM, Christodoulides, M, Carare, RO, Møllgård, K et al.. Acta Neuropathol. 2018;135 (3):363-385. doi: 10.1007/s00401-018-1809-z. PubMed PMID:29368214 .

Inhibition of Aquaporin-4 Improves the Outcome of Ischaemic Stroke and Modulates Brain Paravascular Drainage Pathways. Pirici, I, Balsanu, TA, Bogdan, C, Margaritescu, C, Divan, T et al.. Int J Mol Sci. 2017;19 (1):. doi: 10.3390/ijms19010046. PubMed PMID:29295526 PubMed Central PMC5795996.

Editorial: Clearance Pathways for Amyloid-β. Significance for Alzheimer's Disease and Its Therapy. Carare, RO. Front Aging Neurosci. 2017;9 :339. doi: 10.3389/fnagi.2017.00339. PubMed PMID:29163126 PubMed Central PMC5663857.

The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain. Dobson, H, Sharp, MM, Cumpsty, R, Criswell, TP, Wellman, T et al.. Clin Sci (Lond). 2017;131 (22):2745-2752. doi: 10.1042/CS20171265. PubMed PMID:29021222 .

The structure of the perivascular compartment in the old canine brain: a case study. Criswell, TP, Sharp, MM, Dobson, H, Finucane, C, Weller, RO et al.. Clin Sci (Lond). 2017;131 (22):2737-2744. doi: 10.1042/CS20171278. PubMed PMID:28982724 .

Arterial Pulsations cannot Drive Intramural Periarterial Drainage: Significance for Aβ Drainage. Diem, AK, MacGregor Sharp, M, Gatherer, M, Bressloff, NW, Carare, RO et al.. Front Neurosci. 2017;11 :475. doi: 10.3389/fnins.2017.00475. PubMed PMID:28883786 PubMed Central PMC5574214.

The increasing impact of cerebral amyloid angiopathy: essential new insights for clinical practice. Banerjee, G, Carare, R, Cordonnier, C, Greenberg, SM, Schneider, JA et al.. J Neurol Neurosurg Psychiatry. 2017;88 (11):982-994. doi: 10.1136/jnnp-2016-314697. PubMed PMID:28844070 PubMed Central PMC5740546.

Hypercholesterolemia induced cerebral small vessel disease. Kraft, P, Schuhmann, MK, Garz, C, Jandke, S, Urlaub, D et al.. PLoS One. 2017;12 (8):e0182822. doi: 10.1371/journal.pone.0182822. PubMed PMID:28796818 PubMed Central PMC5552130.

Loss of clusterin shifts amyloid deposition to the cerebrovasculature via disruption of perivascular drainage pathways. Wojtas, AM, Kang, SS, Olley, BM, Gatherer, M, Shinohara, M et al.. Proc Natl Acad Sci U S A. 2017;114 (33):E6962-E6971. doi: 10.1073/pnas.1701137114. PubMed PMID:28701379 PubMed Central PMC5565413.

Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease. Held, F, Morris, AWJ, Pirici, D, Niklass, S, Sharp, MMG et al.. Clin Sci (Lond). 2017;131 (10):1001-1013. doi: 10.1042/CS20170004. PubMed PMID:28348005 .

Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET. de Leon, MJ, Li, Y, Okamura, N, Tsui, WH, Saint-Louis, LA et al.. J Nucl Med. 2017;58 (9):1471-1476. doi: 10.2967/jnumed.116.187211. PubMed PMID:28302766 PubMed Central PMC5577629.

Quantitative Assessment of Cerebral Basement Membranes Using Electron Microscopy. Sharp, MM, Page, A, Morris, A, Weller, RO, Carare, RO et al.. Methods Mol Biol. 2017;1559 :367-375. doi: 10.1007/978-1-4939-6786-5_25. PubMed PMID:28063057 .

Investigating the Lymphatic Drainage of the Brain: Essential Skills and Tools. Albargothy, NJ, Sharp, MM, Gatherer, M, Morris, A, Weller, RO et al.. Methods Mol Biol. 2017;1559 :343-365. doi: 10.1007/978-1-4939-6786-5_24. PubMed PMID:28063056 .

Systems proteomic analysis reveals that clusterin and tissue inhibitor of metalloproteinases 3 increase in leptomeningeal arteries affected by cerebral amyloid angiopathy. Manousopoulou, A, Gatherer, M, Smith, C, Nicoll, JAR, Woelk, CH et al.. Neuropathol Appl Neurobiol. 2017;43 (6):492-504. doi: 10.1111/nan.12342. PubMed PMID:27543695 PubMed Central PMC5638106.

Vascular, glial, and lymphatic immune gateways of the central nervous system. Engelhardt, B, Carare, RO, Bechmann, I, Flügel, A, Laman, JD et al.. Acta Neuropathol. 2016;132 (3):317-38. doi: 10.1007/s00401-016-1606-5. PubMed PMID:27522506 PubMed Central PMC4992028.

Cerebrovascular pathology: the dark side of neurodegeneration. Carare, RO, Kalaria, R. Acta Neuropathol. 2016;131 (5):641-3. doi: 10.1007/s00401-016-1573-x. PubMed PMID:27062259 .

Clearance systems in the brain--implications for Alzheimer diseaser. Tarasoff-Conway, JM, Carare, RO, Osorio, RS, Glodzik, L, Butler, T et al.. Nat Rev Neurol. 2016;12 (4):248. doi: 10.1038/nrneurol.2016.36. PubMed PMID:27020556 .

Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases. Bakker, EN, Bacskai, BJ, Arbel-Ornath, M, Aldea, R, Bedussi, B et al.. Cell Mol Neurobiol. 2016;36 (2):181-94. doi: 10.1007/s10571-015-0273-8. PubMed PMID:26993512 PubMed Central PMC4844641.

Vascular basement membranes as pathways for the passage of fluid into and out of the brain. Morris, AW, Sharp, MM, Albargothy, NJ, Fernandes, R, Hawkes, CA et al.. Acta Neuropathol. 2016;131 (5):725-36. doi: 10.1007/s00401-016-1555-z. PubMed PMID:26975356 PubMed Central PMC4835509.

Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet. Nizari, S, Carare, RO, Hawkes, CA. Sci Rep. 2016;6 :21981. doi: 10.1038/srep21981. PubMed PMID:26911528 PubMed Central PMC4766411.

A Simulation Model of Periarterial Clearance of Amyloid-β from the Brain. Diem, AK, Tan, M, Bressloff, NW, Hawkes, C, Morris, AW et al.. Front Aging Neurosci. 2016;8 :18. doi: 10.3389/fnagi.2016.00018. PubMed PMID:26903861 PubMed Central PMC4751273.

Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer's Disease Mouse Model. Manousopoulou, A, Saito, S, Yamamoto, Y, Al-Daghri, NM, Ihara, M et al.. J Alzheimers Dis. 2016;51 (2):333-8. doi: 10.3233/JAD-151078. PubMed PMID:26836196 PubMed Central PMC4927832.

Pulsations with reflected boundary waves: a hydrodynamic reverse transport mechanism for perivascular drainage in the brain. Coloma, M, Schaffer, JD, Carare, RO, Chiarot, PR, Huang, P et al.. J Math Biol. 2016;73 (2):469-90. doi: 10.1007/s00285-015-0960-6. PubMed PMID:26729476 .

Peristalsis with Oscillating Flow Resistance: A Mechanism for Periarterial Clearance of Amyloid Beta from the Brain. Sharp, MK, Diem, AK, Weller, RO, Carare, RO. Ann Biomed Eng. 2016;44 (5):1553-65. doi: 10.1007/s10439-015-1457-6. PubMed PMID:26399987 .

Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Keable, A, Fenna, K, Yuen, HM, Johnston, DA, Smyth, NR et al.. Biochim Biophys Acta. 2016;1862 (5):1037-46. doi: 10.1016/j.bbadis.2015.08.024. PubMed PMID:26327684 PubMed Central PMC4827375.

Quantification of molecular interactions between ApoE, amyloid-beta (Aβ) and laminin: Relevance to accumulation of Aβ in Alzheimer's disease. Zekonyte, J, Sakai, K, Nicoll, JA, Weller, RO, Carare, RO et al.. Biochim Biophys Acta. 2016;1862 (5):1047-53. doi: 10.1016/j.bbadis.2015.08.025. PubMed PMID:26327683 .

Clearance systems in the brain-implications for Alzheimer disease. Tarasoff-Conway, JM, Carare, RO, Osorio, RS, Glodzik, L, Butler, T et al.. Nat Rev Neurol. 2015;11 (8):457-70. doi: 10.1038/nrneurol.2015.119. PubMed PMID:26195256 PubMed Central PMC4694579.

Does the difference between PART and Alzheimer's disease lie in the age-related changes in cerebral arteries that trigger the accumulation of Aβ and propagation of tau?. Weller, RO, Hawkes, CA, Carare, RO, Hardy, J. Acta Neuropathol. 2015;129 (5):763-6. doi: 10.1007/s00401-015-1416-1. PubMed PMID:25814152 .

Are you also what your mother eats? Distinct proteomic portrait as a result of maternal high-fat diet in the cerebral cortex of the adult mouse. Manousopoulou, A, Woo, J, Woelk, CH, Johnston, HE, Singhania, A et al.. Int J Obes (Lond). 2015;39 (8):1325-8. doi: 10.1038/ijo.2015.35. PubMed PMID:25797609 PubMed Central PMC5399160.

Are the effects of APOE ϵ4 on cognitive function in nonclinical populations age- and gender-dependent?. Rusted, J, Carare, RO. Neurodegener Dis Manag. 2015;5 (1):37-48. doi: 10.2217/nmt.14.43. PubMed PMID:25711453 .

White matter changes in dementia: role of impaired drainage of interstitial fluid. Weller, RO, Hawkes, CA, Kalaria, RN, Werring, DJ, Carare, RO et al.. Brain Pathol. 2015;25 (1):63-78. doi: 10.1111/bpa.12218. PubMed PMID:25521178 PubMed Central PMC8028907.

Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid. Maki, T, Okamoto, Y, Carare, RO, Hase, Y, Hattori, Y et al.. Ann Clin Transl Neurol. 2014;1 (8):519-33. doi: 10.1002/acn3.79. PubMed PMID:25356424 PubMed Central PMC4184555.

Hypertension drives parenchymal β-amyloid accumulation in the brain parenchyma. Bueche, CZ, Hawkes, C, Garz, C, Vielhaber, S, Attems, J et al.. Ann Clin Transl Neurol. 2014;1 (2):124-9. doi: 10.1002/acn3.27. PubMed PMID:25356391 PubMed Central PMC4212487.

Prenatal high-fat diet alters the cerebrovasculature and clearance of β-amyloid in adult offspring. Hawkes, CA, Gentleman, SM, Nicoll, JA, Carare, RO. J Pathol. 2015;235 (4):619-31. doi: 10.1002/path.4468. PubMed PMID:25345857 .

The Cerebrovascular Basement Membrane: Role in the Clearance of β-amyloid and Cerebral Amyloid Angiopathy. Morris, AW, Carare, RO, Schreiber, S, Hawkes, CA. Front Aging Neurosci. 2014;6 :251. doi: 10.3389/fnagi.2014.00251. PubMed PMID:25285078 PubMed Central PMC4168721.

Aβ immunotherapy for Alzheimer's disease: effects on apoE and cerebral vasculopathy. Sakai, K, Boche, D, Carare, R, Johnston, D, Holmes, C et al.. Acta Neuropathol. 2014;128 (6):777-89. doi: 10.1007/s00401-014-1340-9. PubMed PMID:25195061 .

Failure of perivascular drainage of β-amyloid in cerebral amyloid angiopathy. Hawkes, CA, Jayakody, N, Johnston, DA, Bechmann, I, Carare, RO et al.. Brain Pathol. 2014;24 (4):396-403. doi: 10.1111/bpa.12159. PubMed PMID:24946077 PubMed Central PMC8029317.

Impact of N-Acetylcysteine on cerebral amyloid-β plaques and kidney damage in spontaneously hypertensive stroke-prone rats. Bueche, CZ, Garz, C, Stanaszek, L, Niklass, S, Kropf, S et al.. J Alzheimers Dis. 2014;42 Suppl 3 :S305-13. doi: 10.3233/JAD-132615. PubMed PMID:24898644 .

Interplay between age, cerebral small vessel disease, parenchymal amyloid-β, and tau pathology: longitudinal studies in hypertensive stroke-prone rats. Schreiber, S, Drukarch, B, Garz, C, Niklass, S, Stanaszek, L et al.. J Alzheimers Dis. 2014;42 Suppl 3 :S205-15. doi: 10.3233/JAD-132618. PubMed PMID:24825568 .

Intravital imaging in spontaneously hypertensive stroke-prone rats-a pilot study. Niklass, S, Stoyanov, S, Garz, C, Bueche, CZ, Mencl, S et al.. Exp Transl Stroke Med. 2014;6 (1):1. doi: 10.1186/2040-7378-6-1. PubMed PMID:24461046 PubMed Central PMC3996193.

Amyloid and tau in the brain in sporadic Alzheimer's disease: defining the chicken and the egg. Hawkes, CA, Carare, RO, Weller, RO. Acta Neuropathol. 2014;127 (4):617-8. doi: 10.1007/s00401-014-1243-9. PubMed PMID:24452628 PubMed Central PMC3950602.

Immune complex formation impairs the elimination of solutes from the brain: implications for immunotherapy in Alzheimer's disease. Carare, RO, Teeling, JL, Hawkes, CA, Püntener, U, Weller, RO et al.. Acta Neuropathol Commun. 2013;1 :48. doi: 10.1186/2051-5960-1-48. PubMed PMID:24252464 PubMed Central PMC3893559.

Afferent and efferent immunological pathways of the brain. Anatomy, function and failure. Carare, RO, Hawkes, CA, Weller, RO. Brain Behav Immun. 2014;36 :9-14. doi: 10.1016/j.bbi.2013.10.012. PubMed PMID:24145049 .

Stroke-induced opposite and age-dependent changes of vessel-associated markers in co-morbid transgenic mice with Alzheimer-like alterations. Hawkes, CA, Michalski, D, Anders, R, Nissel, S, Grosche, J et al.. Exp Neurol. 2013;250 :270-81. doi: 10.1016/j.expneurol.2013.09.020. PubMed PMID:24103194 .

MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice. Hawkes, CA, Shaw, JE, Brown, M, Sampson, AP, McLaurin, J et al.. Neurodegener Dis. 2014;13 (1):17-23. doi: 10.1159/000351096. PubMed PMID:24021653 .

Review: cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Carare, RO, Hawkes, CA, Jeffrey, M, Kalaria, RN, Weller, RO et al.. Neuropathol Appl Neurobiol. 2013;39 (6):593-611. doi: 10.1111/nan.12042. PubMed PMID:23489283 .

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid-β from the mouse brain. Hawkes, CA, Gatherer, M, Sharp, MM, Dorr, A, Yuen, HM et al.. Aging Cell. 2013;12 (2):224-36. doi: 10.1111/acel.12045. PubMed PMID:23413811 .

Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele. Hawkes, CA, Sullivan, PM, Hands, S, Weller, RO, Nicoll, JA et al.. PLoS One. 2012;7 (7):e41636. doi: 10.1371/journal.pone.0041636. PubMed PMID:22848551 PubMed Central PMC3404985.

Intracerebral immune complex formation induces inflammation in the brain that depends on Fc receptor interaction. Teeling, JL, Carare, RO, Glennie, MJ, Perry, VH. Acta Neuropathol. 2012;124 (4):479-90. doi: 10.1007/s00401-012-0995-3. PubMed PMID:22618994 PubMed Central PMC3444701.

Spiritual belief, social support, physical functioning and depression among older people in Bulgaria and Romania. Coleman, PG, Carare, RO, Petrov, I, Forbes, E, Saigal, A et al.. Aging Ment Health. 2011;15 (3):327-33. doi: 10.1080/13607863.2010.519320. PubMed PMID:21491217 .

Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Hawkes, CA, Härtig, W, Kacza, J, Schliebs, R, Weller, RO et al.. Acta Neuropathol. 2011;121 (4):431-43. doi: 10.1007/s00401-011-0801-7. PubMed PMID:21259015 .

Location of the sural nerve during posterolateral approach to the ankle. Jowett, AJ, Sheikh, FT, Carare, RO, Goodwin, MI. Foot Ankle Int. 2010;31 (10):880-3. doi: 10.3113/FAI.2010.0880. PubMed PMID:20964966 .

Pathophysiology of the lymphatic drainage of the central nervous system: Implications for pathogenesis and therapy of multiple sclerosis. Weller, RO, Galea, I, Carare, RO, Minagar, A. Pathophysiology. 2010;17 (4):295-306. doi: 10.1016/j.pathophys.2009.10.007. PubMed PMID:19954936 .

Cervical lymph nodes are found in direct relationship with the internal carotid artery: significance for the lymphatic drainage of the brain. Clapham, R, O'Sullivan, E, Weller, RO, Carare, RO. Clin Anat. 2010;23 (1):43-7. doi: 10.1002/ca.20887. PubMed PMID:19918869 .

Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer disease. Weller, RO, Preston, SD, Subash, M, Carare, RO. Alzheimers Res Ther. 2009;1 (2):6. doi: 10.1186/alzrt6. PubMed PMID:19822028 PubMed Central PMC2874258.

Population studies of sporadic cerebral amyloid angiopathy and dementia: a systematic review. Keage, HA, Carare, RO, Friedland, RP, Ince, PG, Love, S et al.. BMC Neurol. 2009;9 :3. doi: 10.1186/1471-2377-9-3. PubMed PMID:19144113 PubMed Central PMC2647900.

Lymphatic drainage of the brain and the pathophysiology of neurological disease. Weller, RO, Djuanda, E, Yow, HY, Carare, RO. Acta Neuropathol. 2009;117 (1):1-14. doi: 10.1007/s00401-008-0457-0. PubMed PMID:19002474 .

A unique variation of the sciatic nerve. Carare, RO, Goodwin, M. Clin Anat. 2008;21 (8):800-1. doi: 10.1002/ca.20696. PubMed PMID:18773477 .

Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer's disease. Weller, RO, Subash, M, Preston, SD, Mazanti, I, Carare, RO et al.. Brain Pathol. 2008;18 (2):253-66. doi: 10.1111/j.1750-3639.2008.00133.x. PubMed PMID:18363936 PubMed Central PMC8095597.

Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology. Carare, RO, Bernardes-Silva, M, Newman, TA, Page, AM, Nicoll, JA et al.. Neuropathol Appl Neurobiol. 2008;34 (2):131-44. doi: 10.1111/j.1365-2990.2007.00926.x. PubMed PMID:18208483 .

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Bio

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Roxana Carare is a medically qualified Professor of Clinical Neuroanatomy and experimental neuropathology in the University of Southampton. Having graduated in general medicine in 1994 in Bucharest, Roxana completed her PhD in experimental neuropathology in 2006, in the University of Southampton, UK. The main international recognition for Roxana Carare has come from the neuroanatomy and neuropathology interdisciplinary research she leads, demonstrating the unique lymphatic drainage pathways by which fluid and soluble amyloid are eliminated from the brain along basement membranes within the walls of cerebral capillaries and arteries (Intramural Periarterial Drainage Pathways, IPAD). The focus of her research is to manipulate the pathways to improve the clearance of amyloid and interstitial fluid from the ageing brain, preventing neurodegenerative and neurovascular disease.

Roxana is currently a communications Co-Chair for Alliance of Women Alzheimer's Researches (AWARE)

Professor Roy weller

PRINCIPAL INVESTIGATOR

Roy’s main area of research has been in the pathophysiology of fluid drainage pathways from the CNS and perivascular lymphatic drainage.

row@soton.ac.uk

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Publications

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Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review. Rasschaert, M, Weller, RO, Schroeder, JA, Brochhausen, C, Idée, JM et al.. J Magn Reson Imaging. 2020;52 (5):1293-1305. doi: 10.1002/jmri.27124. PubMed PMID:32246802 PubMed Central PMC7687192.

Microvasculature changes and cerebral amyloid angiopathy in Alzheimer's disease and their potential impact on therapy. Weller, RO, Boche, D, Nicoll, JA. Acta Neuropathol. 2009;118 (1):87-102. doi: 10.1007/s00401-009-0498-z. PubMed PMID:19234858 .

Consequence of Abeta immunization on the vasculature of human Alzheimer's disease brain. Boche, D, Zotova, E, Weller, RO, Love, S, Neal, JW et al.. Brain. 2008;131 (Pt 12):3299-310. doi: 10.1093/brain/awn261. PubMed PMID:18953056 .

Immunotherapy for Alzheimer's disease and other dementias. Boche, D, Nicoll, JA, Weller, RO. Clin Neuropharmacol. ;29 (1):22-7. doi: 10.1097/00002826-200601000-00008. PubMed PMID:16518131 .

Immunotherapy for Alzheimer's disease and other dementias. Boche, D, Nicoll, JA, Weller, RO. Curr Opin Neurol. 2005;18 (6):720-5. doi: 10.1097/01.wco.0000191513.60368.a7. PubMed PMID:16280685 .

Cerebrovascular disease and the pathophysiology of Alzheimer's disease. Implications for therapy. Weller, RO, Cohen, NR, Nicoll, JA. Panminerva Med. 2004;46 (4):239-51. . PubMed PMID:15876980 .

Cytokine-induced enhancement of autoimmune inflammation in the brain and spinal cord: implications for multiple sclerosis. Sun, D, Newman, TA, Perry, VH, Weller, RO. Neuropathol Appl Neurobiol. 2004;30 (4):374-84. doi: 10.1111/j.1365-2990.2003.00546.x. PubMed PMID:15305983 .

Cerebral amyloid angiopathy plays a direct role in the pathogenesis of Alzheimer's disease. Pro-CAA position statement. Nicoll, JA, Yamada, M, Frackowiak, J, Mazur-Kolecka, B, Weller, RO et al.. Neurobiol Aging. ;25 (5):589-97; discussion 603-4. doi: 10.1016/j.neurobiolaging.2004.02.003. PubMed PMID:15172734 .

Different meningitis-causing bacteria induce distinct inflammatory responses on interaction with cells of the human meninges. Fowler, MI, Weller, RO, Heckels, JE, Christodoulides, M. Cell Microbiol. 2004;6 (6):555-67. doi: 10.1111/j.1462-5822.2004.00382.x. PubMed PMID:15104596 .

Cerebral amyloid angiopathy: pathogenesis and effects on the ageing and Alzheimer brain. Weller, RO, Nicoll, JA. Neurol Res. 2003;25 (6):611-6. doi: 10.1179/016164103101202057. PubMed PMID:14503015 .

A new role for astrocytes: beta-amyloid homeostasis and degradation. Nicoll, JA, Weller, RO. Trends Mol Med. 2003;9 (7):281-2. doi: 10.1016/s1471-4914(03)00109-6. PubMed PMID:12900213 .

Capillary and arterial cerebral amyloid angiopathy in Alzheimer's disease: defining the perivascular route for the elimination of amyloid beta from the human brain. Preston, SD, Steart, PV, Wilkinson, A, Nicoll, JA, Weller, RO et al.. Neuropathol Appl Neurobiol. 2003;29 (2):106-17. doi: 10.1046/j.1365-2990.2003.00424.x. PubMed PMID:12662319 .

Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nicoll, JA, Wilkinson, D, Holmes, C, Steart, P, Markham, H et al.. Nat Med. 2003;9 (4):448-52. doi: 10.1038/nm840. PubMed PMID:12640446 .

Cerebrovascular disease is a major factor in the failure of elimination of Abeta from the aging human brain: implications for therapy of Alzheimer's disease. Weller, RO, Yow, HY, Preston, SD, Mazanti, I, Nicoll, JA et al.. Ann N Y Acad Sci. 2002;977 :162-8. doi: 10.1111/j.1749-6632.2002.tb04812.x. PubMed PMID:12480747 .

Interaction of Neisseria meningitidis with human meningeal cells induces the secretion of a distinct group of chemotactic, proinflammatory, and growth-factor cytokines. Christodoulides, M, Makepeace, BL, Partridge, KA, Kaur, D, Fowler, MI et al.. Infect Immun. 2002;70 (8):4035-44. doi: 10.1128/IAI.70.8.4035-4044.2002. PubMed PMID:12117909 PubMed Central PMC128145.

The spectrum of vascular disease in dementia. From ischaemia to amyloid angiopathy. Weller, RO, Preston, SD. Adv Exp Med Biol. 2001;487 :111-22. doi: 10.1007/978-1-4615-1249-3_9. PubMed PMID:11403152 .

How well does the CSF inform upon pathology in the brain in Creutzfeldt-Jakob and Alzheimer's diseases?. Weller, RO. J Pathol. 2001;194 (1):1-3. doi: 10.1002/1096-9896(200105)194:1<1::AID-PATH871>3.0.CO;2-M. PubMed PMID:11329133 .

XlVth International Congress of Neuropathology, 3-6 September, 2000, Birmingham, United Kingdom. Weller, RO. Brain Pathol. 2001;11 (2):250-8. doi: 10.1111/j.1750-3639.2001.tb00396.x. PubMed PMID:11303799 PubMed Central PMC8098362.

Role of chemokines, neuronal projections, and the blood-brain barrier in the enhancement of cerebral EAE following focal brain damage. Sun, D, Tani, M, Newman, TA, Krivacic, K, Phillips, M et al.. J Neuropathol Exp Neurol. 2000;59 (12):1031-43. doi: 10.1093/jnen/59.12.1031. PubMed PMID:11138923 .

Interactions of Neisseria meningitidis with cells of the human meninges. Hardy, SJ, Christodoulides, M, Weller, RO, Heckels, JE. Mol Microbiol. 2000;36 (4):817-29. doi: 10.1046/j.1365-2958.2000.01923.x. PubMed PMID:10844670 .

Cerebral amyloid angiopathy: accumulation of A beta in interstitial fluid drainage pathways in Alzheimer's disease. Weller, RO, Massey, A, Kuo, YM, Roher, AE. Ann N Y Acad Sci. 2000;903 :110-7. doi: 10.1111/j.1749-6632.2000.tb06356.x. PubMed PMID:10818495 .

Lymphocyte targeting of the brain in adoptive transfer cryolesion-EAE. Lake, J, Weller, RO, Phillips, MJ, Needham, M. J Pathol. 1999;187 (2):259-65. doi: 10.1002/(SICI)1096-9896(199901)187:2<259::AID-PATH212>3.0.CO;2-H. PubMed PMID:10365103 .

Pathology of cerebrospinal fluid and interstitial fluid of the CNS: significance for Alzheimer disease, prion disorders and multiple sclerosis. Weller, RO. J Neuropathol Exp Neurol. 1998;57 (10):885-94. doi: 10.1097/00005072-199810000-00001. PubMed PMID:9786239 .

Cerebral amyloid angiopathy: amyloid beta accumulates in putative interstitial fluid drainage pathways in Alzheimer's disease. Weller, RO, Massey, A, Newman, TA, Hutchings, M, Kuo, YM et al.. Am J Pathol. 1998;153 (3):725-33. doi: 10.1016/s0002-9440(10)65616-7. PubMed PMID:9736023 PubMed Central PMC1853019.

Role of cervical lymph nodes in autoimmune encephalomyelitis in the Lewis rat. Phillips, MJ, Needham, M, Weller, RO. J Pathol. 1997;182 (4):457-64. doi: 10.1002/(SICI)1096-9896(199708)182:4<457::AID-PATH870>3.0.CO;2-Y. PubMed PMID:9306968 .

Subarachnoid haemorrhage and myths about saccular aneurysms. Weller, RO. J Clin Pathol. 1995;48 (12):1078-81. doi: 10.1136/jcp.48.12.1078. PubMed PMID:8567990 PubMed Central PMC503030.

Focal brain damage enhances experimental allergic encephalomyelitis in brain and spinal cord. Phillips, MJ, Weller, RO, Kida, S, Iannotti, F. Neuropathol Appl Neurobiol. 1995;21 (3):189-200. doi: 10.1111/j.1365-2990.1995.tb01050.x. PubMed PMID:7477727 .

Enhancement of microglial activity in brain and spinal cord in autoimmune encephalomyelitis. Phillips, M, Kida, S, Steart, PV, Iannotti, F, Weller, RO et al.. Neuropathol Appl Neurobiol. 1994;20 (2):201-2. . PubMed PMID:8072662 .

CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Kida, S, Pantazis, A, Weller, RO. Neuropathol Appl Neurobiol. 1993;19 (6):480-8. doi: 10.1111/j.1365-2990.1993.tb00476.x. PubMed PMID:7510047 .

Brain damage after profoundly hypothermic circulatory arrest: correlations between neurophysiologic and neuropathologic findings. An experimental study in vertebrates. Fessatidis, IT, Thomas, VL, Shore, DF, Sedgwick, ME, Hunt, RH et al.. J Thorac Cardiovasc Surg. 1993;106 (1):32-41. . PubMed PMID:8321003 .

Neuropathological features of profoundly hypothermic circulatory arrest: an experimental study in the pig. Fessatidis, IT, Thomas, VL, Shore, DF, Hunt, RH, Weller, RO et al.. Cardiovasc Surg. 1993;1 (2):155-60. . PubMed PMID:8076019 .

Expression of the p53 protein in a spectrum of astrocytic tumours. Ellison, DW, Gatter, KC, Steart, PV, Lane, DP, Weller, RO et al.. J Pathol. 1992;168 (4):383-6. doi: 10.1002/path.1711680408. PubMed PMID:1336544 .

Directional and compartmentalised drainage of interstitial fluid and cerebrospinal fluid from the rat brain. Zhang, ET, Richards, HK, Kida, S, Weller, RO. Acta Neuropathol. 1992;83 (3):233-9. doi: 10.1007/BF00296784. PubMed PMID:1373020 .

Grading of brain tumours. The British experience. Weller, RO. Neurosurg Rev. 1992;15 (1):7-11. doi: 10.1007/BF02352059. PubMed PMID:1316572 .

The structure of the lamina cribrosa of the human eye: an immunocytochemical and electron microscopical study. Elkington, AR, Inman, CB, Steart, PV, Weller, RO. Eye (Lond). 1990;4 ( Pt 1) :42-57. doi: 10.1038/eye.1990.5. PubMed PMID:2182351 .

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Bio

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Roy Weller qualified in Medicine at Guy’s Hospital, London. Following research and clinical pathology posts in London and New York, he was appointed Professor of Neuropathology in the University of Southampton UK to provide a clinical diagnostic neuropathology service and to pursue research.

Roy’s main area of research has been in the pathophysiology of fluid drainage pathways from the CNS. Initially the research involved hydrocephalus and lymphatic drainage of CSF but later concentrated on the perivascular lymphatic drainage of Interstitial Fluid and Soluble Metabolites from the brain, correlating experimental models with the pathology of human neuroimmunological disease and dementias. There is growing acceptance that failure of perivascular elimination of amyloid-beta (Aß) from the brain along the walls of ageing cerebral arteries plays a significant role in the aetiology of Alzheimer’s disease and cerebral amyloid angiopathy. The aim is to develop a broadly based translational approach to perivascular drainage of the brain and the origin of Neuro-ophthalmological disease in the search for treatment of dementias and neuroimmunological disorders.

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Dr Louise Kelly

RESEARCH FELLOW

Investigating the role of air pollution in the progression of Neurological diseases.

l.kelly@soton.ac.uk

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Publications

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Identification of intraneuronal amyloid beta oligomers in locus coeruleus neurons of Alzheimer's patients and their potential impact on inhibitory neurotransmitter receptors and neuronal excitability. Kelly, L, Seifi, M, Ma, R, Mitchell, SJ, Rudolph, U et al.. Neuropathol Appl Neurobiol. 2021;47 (4):488-505. doi: 10.1111/nan.12674. PubMed PMID:33119191 .

Dynamic Modulation of Mouse Locus Coeruleus Neurons by Vasopressin 1a and 1b Receptors. Campos-Lira, E, Kelly, L, Seifi, M, Jackson, T, Giesecke, T et al.. Front Neurosci. 2018;12 :919. doi: 10.3389/fnins.2018.00919. PubMed PMID:30618551 PubMed Central PMC6295453.

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Dr Christopher Brown

RESEARCH FELLOW

Testing proprietary synthetic peptide immunogens for active immunisation against tau protein

c.m.brown@soton.ac.uk

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Publications

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Glucocorticoids activate a synapse weakening pathway culminating in tau phosphorylation in the hippocampus. Yi JH, Brown C, Whitehead G, Piers T, Lee YS, Perez CM, Regan P, Whitcomb DJ, Cho K. Pharmacol Res. 2017 Jul;121:42-51. doi: 10.1016/j.phrs.2017.04.015. Epub 2017 Apr 14. PMID: 28416463.

Microtubule-associated protein tau is essential for long-term depression in the hippocampus. Kimura T, Whitcomb DJ, Jo J, Regan P, Piers T, Heo S, Brown C, Hashikawa T, Murayama M, Seok H, Sotiropoulos I, Kim E, Collingridge GL, Takashima A, Cho K. Philos Trans R Soc Lond B Biol Sci. 2013 Dec 2;369(1633):20130144. doi: 10.1098/rstb.2013.0144. PMID: 24298146.

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Bio

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Dr Jennifer Dewing

RESEARCH FELLOW

Evaluating the expression of the enzyme stearoyl-CoA desaturase (SCD) in neurodegenerative disease.

jmd2g08@soton.ac.uk

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Publications

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In vitro stem cell modelling demonstrates a proof-of-concept for excess functional mutant TIMP3 as the cause of Sorsby fundus dystrophy. Hongisto, H, Dewing, JM, Christensen, DR, Scott, J, Cree, AJ et al.. J Pathol. 2020;252 (2):138-150. doi: 10.1002/path.5506. PubMed PMID:32666594 .

Autism Spectrum Disorders: Multiple Routes to, and Multiple Consequences of, Abnormal Synaptic Function and Connectivity. Carroll, L, Braeutigam, S, Dawes, JM, Krsnik, Z, Kostovic, I et al.. Neuroscientist. 2021;27 (1):10-29. doi: 10.1177/1073858420921378. PubMed PMID:32441222 PubMed Central PMC7804368.

Expression and localisation of thymosin beta-4 in the developing human early fetal heart. Saunders, V, Dewing, JM, Sanchez-Elsner, T, Wilson, DI. PLoS One. 2018;13 (11):e0207248. doi: 10.1371/journal.pone.0207248. PubMed PMID:30412598 PubMed Central PMC6226193.

A convenient protocol for establishing a human cell culture model of the outer retina. Lynn, SA, Keeling, E, Dewing, JM, Johnston, DA, Page, A et al.. F1000Res. 2018;7 :1107. doi: 10.12688/f1000research.15409.1. PubMed PMID:30271583 PubMed Central PMC6137423.

Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory. Gould, JM, Smith, PJ, Airey, CJ, Mort, EJ, Airey, LE et al.. Proc Natl Acad Sci U S A. 2018;115 (31):E7398-E7407. doi: 10.1073/pnas.1721876115. PubMed PMID:29941596 PubMed Central PMC6077736.

AMMECR1: a single point mutation causes developmental delay, midface hypoplasia and elliptocytosis. Andreoletti, G, Seaby, EG, Dewing, JM, O'Kelly, I, Lachlan, K et al.. J Med Genet. 2017;54 (4):269-277. doi: 10.1136/jmedgenet-2016-104100. PubMed PMID:27811305 PubMed Central PMC5502304.

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Maureen Gatherer

SENIOR RESEARCH TECHNICIAN

Investigating the link between loss of perivascular innervation by cholinergic neurons and cerebral amyloid angiopathy.

m.gatherer@soton.ac.uk

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Publications

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A High Fat "Western-style" Diet Induces AMD-Like Features in Wildtype Mice. Keeling, E, Lynn, SA, Koh, YM, Scott, JA, Kendall, A et al.. Mol Nutr Food Res. 2022;66 (11):e2100823. doi: 10.1002/mnfr.202100823. PubMed PMID:35306732 .

A lasered mouse model of retinal degeneration displays progressive outer retinal pathology providing insights into early geographic atrophy. Ibbett, P, Goverdhan, SV, Pipi, E, Chouhan, JK, Keeling, E et al.. Sci Rep. 2019;9 (1):7475. doi: 10.1038/s41598-019-43906-z. PubMed PMID:31097765 PubMed Central PMC6522499.

AAV2/8 Anti-angiogenic Gene Therapy Using Single-Chain Antibodies Inhibits Murine Choroidal Neovascularization. Hughes, CP, O'Flynn, NMJ, Gatherer, M, McClements, ME, Scott, JA et al.. Mol Ther Methods Clin Dev. 2019;13 :86-98. doi: 10.1016/j.omtm.2018.11.005. PubMed PMID:30719487 PubMed Central PMC6350388.

Rat astrocytic tumour cells are associated with an anti-inflammatory microglial phenotype in an organotypic model. Billingham, C, Powell, MR, Jenner, KA, Johnston, DA, Gatherer, M et al.. Neuropathol Appl Neurobiol. 2013;39 (3):243-55. doi: 10.1111/j.1365-2990.2012.01283.x. PubMed PMID:22631872 .

Aberrant Timm-stained fibres in the dentate gyrus following tetanus toxin-induced seizures in the rat. Mitchell, J, Gatherer, M, Sundstrom, LE. Neuropathol Appl Neurobiol. 1996;22 (2):129-35. . PubMed PMID:8732188 .

Hippocampal NPY neurons project to the fascia dentata in organotypic cultures. Mitchell, J, Gatherer, M, Best, N, Sundstrom, L, Wheal, HV et al.. Hippocampus. 1996;6 (2):173-82. doi: 10.1002/(SICI)1098-1063(1996)6:2<173::AID-HIPO7>3.0.CO;2-Q. PubMed PMID:8797017 .

Loss of hilar somatostatin neurons following tetanus toxin-induced seizures. Mitchell, J, Gatherer, M, Sundstrom, LE. Acta Neuropathol. 1995;89 (5):425-30. doi: 10.1007/BF00307647. PubMed PMID:7542423 .

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