Imperial College London

DrRonaldPearce

Faculty of MedicineFaculty of Medicine Centre

Honorary Clinical Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 3311 7361ronald.pearce

 
 
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Assistant

 

Dr Stavia Blunt +44 (0)20 8846 1182

 
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Location

 

10L16Charing Cross HospitalCharing Cross Campus

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Summary

 

Publications

Publication Type
Year
to

97 results found

Patel S, Tilley B, Pearce RKB, Gentleman Set al., 2020, A clinicopathological investigation of brainstem nuclei in dementia with Lewy bodies and Parkinson's disease dementia, 121st Meeting of the British-Neuropathological-Society / Developmental Neuropathology Symposium, Publisher: WILEY, Pages: 19-20, ISSN: 0305-1846

Conference paper

Liu AKL, Lim YM, Pearce RKB, Gentleman SMet al., 2019, DO ANTICHOLINERGIC DRUGS INCREASE ALZHEIMER'S PATHOLOGY IN PARKINSON'S PATIENTS? A RETROSPECTIVE POST-MORTEM INVESTIGATION, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, Pages: E17-E17, ISSN: 0022-3050

Conference paper

Liu AKL, Lim YM, Pearce RKB, Gentleman SMet al., 2019, DO ANTICHOLINERGIC DRUGS INCREASE ALZHEIMER'S PATHOLOGY IN PARKINSON'S PATIENTS? A RETROSPECTIVE POST-MORTEM INVESTIGATION, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, Pages: E20-E20, ISSN: 0022-3050

Conference paper

Alexandris AS, Walker L, Liu AKL, McAleese KE, Johnson M, Pearce RKB, Gentleman SM, Attems Jet al., 2019, Cholinergic deficits and galaninergic hyperinnervation of the nucleus basalis of Meynert in Alzheimer's disease and Lewy body disorders, NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol: 46, Pages: 264-278, ISSN: 0305-1846

Journal article

Williams MR, Sharma P, Macdonald C, Pearce RKB, Hirsch SR, Maier Met al., 2019, Axonal myelin decrease in the splenium in major depressive disorder, EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, Vol: 269, Pages: 387-395, ISSN: 0940-1334

Journal article

Liu KL, Chau TW, Lim EJ, Ahmed I, Chang R, Kalaitzakis M, Graeber M, Gentleman S, Pearce Ret al., 2019, Hippocampal CA2 Lewy pathology is associated with cholinergic degeneration in Parkinson’s disease with cognitive decline, Acta Neuropathologica Communications, Vol: 7, ISSN: 2051-5960

Although the precise neuropathological substrates of cognitive decline in Parkinson’s disease (PD) remain elusive, it has long been regarded that pathology in the CA2 hippocampal subfield is characteristic of Lewy body dementias, including dementia in PD (PDD). Early non-human primate tracer studies demonstrated connections from the nucleus of the vertical limb of the diagonal band of Broca (nvlDBB, Ch2) to the hippocampus. However, the relationship between Lewy pathology of the CA2 subfield and cholinergic fibres has not been explored. Therefore, in this study, we investigated the burden of pathology in the CA2 subsector of PD cases with varying degrees of cognitive impairment and correlated this with the extent of septohippocampal cholinergic deficit. Hippocampal sections from 67 PD, 34 PD with mild cognitive impairment and 96 PDD cases were immunostained for tau and alpha-synuclein, and the respective pathology burden was assessed semi-quantitatively. In a subset of cases, the degree of CA2 cholinergic depletion was quantified using confocal microscopy and correlated with cholinergic neuronal loss in Ch2. We found that only cases with dementia have a significantly greater Lewy pathology, whereas cholinergic fibre depletion was evident in cases with mild cognitive impairment and this was significantly correlated with loss of cholinergic neurons in Ch2. In addition, multiple antigen immunofluorescence demonstrated colocalisation between cholinergic fibres and alpha-synuclein but not tau pathology. Such specific Lewy pathology targeting the cholinergic system within the CA2 subfield may contribute to the unique memory retrieval deficit seen in patients with Lewy body disorders, as distinct from the memory storage deficit seen in Alzheimer’s disease.

Journal article

Tilley BS, Goldfinger MH, Pearce RKB, Gentleman SMet al., 2019, The neuropathology of motor subtypes of Parkinson's disease: from the brainstem to basal ganglia, 19th International Congress of Neuropathology, Publisher: WILEY, Pages: 132-132, ISSN: 1015-6305

Conference paper

Liu AKL, Lim EJ, Ahmed I, Chang RC-C, Pearce RKB, Gentleman SMet al., 2018, Review: revisiting the human cholinergic nucleus of the diagonal band of Broca, Neuropathology and Applied Neurobiology, Vol: 44, Pages: 647-662, ISSN: 0305-1846

Although the nucleus of the vertical limb of the diagonal band of Broca (nvlDBB) is the second largest cholinergic nucleus in the basal forebrain, after the nucleus basalis of Meynert (nbM), it has not generally been a focus for studies of neurodegenerative disorders. However, the nvlDBB does have an important projection to the hippocampus and discrete lesions of the rostral basal forebrain have been shown to disrupt retrieval memory function, a major deficit seen in patients with Lewy body disorders. One reason for its neglect is that the anatomical boundaries of the nvlDBB are ill defined and this area of the brain is not part of routine diagnostic sampling protocols. We have reviewed the history and anatomy of the nvlDBB and now propose guidelines for distinguishing nvlDBB from other neighbouring cholinergic cell groups for standardising future clinicopathological work. Thorough review of the literature regarding neurodegenerative conditions reveals inconsistent results in terms of cholinergic neuronal loss within the nvlDBB. This is likely to be due to the use of variable neuronal inclusion criteria and omission of cholinergic immunohistochemical markers. Extrapolating from those studies showing significant nvlDBB neuronal loss in Lewy body dementia, we propose an anatomical and functional connection between the cholinergic component of the nvlDBB (Ch2) and the CA2 subfield in the hippocampus which may be especially vulnerable in Lewy body disorders. This article is protected by copyright. All rights reserved.

Journal article

Tilley B, Goldfinger M, Pearce R, Gentleman Set al., 2018, Locus coeruleus pathology illustrates a continuum of lewy body dementia, 119th Meeting of the British-Neuropathological-Society (BNS) / Epilepsy Neuropathology Symposium, Publisher: WILEY, Pages: 14-15, ISSN: 0305-1846

Conference paper

Chau TW, Liu AKL, Lim EJ, Ahmed I, Pearce RKB, Gentleman SMet al., 2017, Cognitive decline and hippocampal CA2 pathology in Lewy body disorders, 118th Meeting of the British-Neuropathological-Society, Publisher: WILEY, Pages: 11-12, ISSN: 0305-1846

Conference paper

Alexandris A, Walker L, Liu AKL, Pearce RKB, Gentleman SM, Attems Jet al., 2017, Differential expression of galanin in the cholinergic basal forebrain in Lewy body disorders and Alzheimer's disease, 118th Meeting of the British-Neuropathological-Society, Publisher: WILEY, Pages: 12-12, ISSN: 0305-1846

Conference paper

Liu K, Goldfinger MH, Questari HE, Pearce RKB, Gentleman SMet al., 2016, ARTAG in the basal forebrain: Widening the constellation of astrocytic tau pathology, Acta Neuropathologica Communications, Vol: 4, ISSN: 2051-5960

Journal article

Williams MR, Pattni S, Pearce RK, Hirsch SR, Maier Met al., 2016, Basolateral but not corticomedial amygdala shows neuroarchitectural changes in schizophrenia, JOURNAL OF NEUROSCIENCE RESEARCH, Vol: 94, Pages: 544-547, ISSN: 0360-4012

Journal article

Questari HE, Liu AKL, Pearce RKB, Gentleman SMet al., 2016, Chronic traumatic encephalopathy-like changes within the basal forebrain among cases in the Parkinson's UK Tissue Bank, 117th Meeting of the British-Neuropathological-Society, Publisher: WILEY-BLACKWELL, Pages: 39-39, ISSN: 0305-1846

Conference paper

Lim EJ, Liu AKL, Ahmed I, Pearce RKB, Gentleman SMet al., 2016, Clinicopathological correlations of the nucleus of the diagonal band of Broca in Lewy body disorders, 117th Meeting of the British-Neuropathological-Society, Publisher: WILEY, Pages: 12-13, ISSN: 0305-1846

Conference paper

Liu AKL, Hurry MED, Ng OTW, DeFelice J, Lai HM, Pearce RKB, Wong GTC, Chang RCC, Gentleman SMet al., 2015, Bringing CLARITY to the human brain: visualization of Lewy pathology in three dimensions, Neuropathology and Applied Neurobiology, Vol: 42, Pages: 573-587, ISSN: 1365-2990

Aims: CLARITY is a novel technique which enables three-dimensional visualisation of immunostained tissue for the study of circuitry and spatial interactions between cells and molecules in the brain. In this study we aimed to compare methodological differences in the application of CLARITY between rodent and large human post-mortem brain samples. In addition, we aimed to investigate if this technique could be used to visualise Lewy pathology in a post-mortem Parkinson’s brain. Methods: Rodent and human brain samples were clarified and immunostained using the passive version of the CLARITY technique. Samples were then immersed in different refractive index matching media before mounting and visualising under a confocal microscope. Results: We found that tissue clearing speed using passive CLARITY differs according to species (human vs rodents), brain region and degree of fixation (fresh vs formalin-fixed tissues). Furthermore, there were advantages to using specific refractive index matching media. We have applied this technique and have successfully visualised Lewy body inclusions in three dimensions within the nucleus basalis of Meynert, and the spatial relationship between monoaminergic fibres and Lewy pathologies among nigrostriatal fibres in the midbrain without the need for physical serial sectioning of brain tissue. Conclusions: The effective use of CLARITY on large samples of human tissue opens up many potential avenues for detailed pathological and morphological studies.

Journal article

Alexandris A, Liu AKL, Chang RCC, Pearce RKB, Gentleman Set al., 2015, Differential expression of galanin in the cholinergic basal forebrain of patients with Lewy body disorders., Acta Neuropathologica Communications, Vol: 3, ISSN: 2051-5960

IntroductionDepletion of cholinergic neurons within the nucleus basalis of Meynert (nbM) is thought to contribute to the development of cognitive impairments in both Alzheimer’s disease (AD) and Lewy body disorders (LBD). It has been reported that, in late stage AD, a network of fibres that contain the neuropeptide galanin displays significant hypertrophy and ‘hyperinnervates’ the surviving cholinergic neurons. Galanin is considered as a highly inducible neuroprotective factor and in AD this is assumed to be part of a protective tissue response. The aim of this study was to determine if a similar galanin upregulation is present in the nbM in post-mortem tissue from patients with LBD. Gallatin immunohistochemistry was carried out on anterior nbM sections from 76 LBD cases (27 PD, 15 PD with mild cognitive impairment (MCI), 34 PD with dementia (PDD) and 4 aged-matched controls. Galaninergic innervation of cholinergic neurons was assessed on a semi-quantitative scale.ResultsThe LBD group had significantly higher galaninergic innervation scores (p = 0.016) compared to controls. However, this difference was due to increased innervation density only in a subgroup of LBD cases and this correlated positively with choline acetyltransferase–immunopositive neuron density.ConclusionGalanin upregulation within the basal forebrain cholinergic system in LBD, similar to that seen in AD, may represent an intrinsic adaptive response to neurodegeneration that is consistent with its proposed roles in neurogenesis and neuroprotection.

Journal article

Williams MR, Sharma P, Fung KL, Pearce RKB, Hirsch SR, Maier Met al., 2015, Axonal myelin increase in the callosal genu in depression but not schizophrenia, PSYCHOLOGICAL MEDICINE, Vol: 45, Pages: 2145-2155, ISSN: 0033-2917

Journal article

Liu AKL, Chang RC-C, Pearce RKB, Gentleman SMet al., 2015, Nucleus basalis of Meynert revisited: anatomy, history and differential involvement in Alzheimer's and Parkinson's disease, ACTA NEUROPATHOLOGICA, Vol: 129, Pages: 527-540, ISSN: 0001-6322

Journal article

Liu AKL, Chang RCC, Pearce RKB, Gentleman SMet al., 2015, Sub-regional nucleus basalis of Meynert pathology in Lewy body disorders, 116th Meeting of the British-Neuropathological-Society, Publisher: WILEY-BLACKWELL, Pages: 11-12, ISSN: 0305-1846

Conference paper

Alexandris A, Liu AKL, Pearce RKB, Gentleman SMet al., 2015, Differential expression of galanin in the basal forebrain in Lewy body disorders, 116th Meeting of the British-Neuropathological-Society, Publisher: WILEY-BLACKWELL, Pages: 34-34, ISSN: 0305-1846

Conference paper

Liu AKL, Chang RCC, Pearce RKB, Gentleman SMet al., 2015, Where is the human nucleus basalis of Meynert?, 116th Meeting of the British-Neuropathological-Society, Publisher: WILEY-BLACKWELL, Pages: 34-35, ISSN: 0305-1846

Conference paper

Williams MR, Galvin K, O'Sullivan B, MacDonald CD, Ching EWK, Turkheimer F, Howes OD, Pearce RKB, Hirsch SR, Maier Met al., 2014, Neuropathological changes in the substantia nigra in schizophrenia but not depression, EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, Vol: 264, Pages: 285-296, ISSN: 0940-1334

Journal article

Williams M, Pearce RKB, Hirsch SR, Ansorge O, Thom M, Maier Met al., 2014, Fibrillary astrocytes are decreased in the subgenual cingulate in schizophrenia, EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, Vol: 264, Pages: 357-362, ISSN: 0940-1334

Journal article

Liu AKL, Pearce RKB, Gentleman SM, 2014, Assessing cortical cholinergic projections in Lewy body disorders using M2 muscarinic receptor immunohistochemistry, 115th Meeting of the British-Neuropathological-Society, Institute-of-Child-Health, Publisher: WILEY-BLACKWELL, Pages: 37-38, ISSN: 0305-1846

Conference paper

Vivekanantham S, Gentleman SM, Pearce RKB, Nandi Det al., 2014, Challenges in histological identification of the pedunculopontine nucleus, 115th Meeting of the British-Neuropathological-Society, Institute-of-Child-Health, Publisher: WILEY-BLACKWELL, Pages: 39-40, ISSN: 0305-1846

Conference paper

Pey P, Pearce RKB, Kalaitzakis ME, Griffin WST, Gentleman SMet al., 2014, Phenotypic profile of alternative activation marker CD163 is different in Alzheimer's and Parkinson's disease, ACTA NEUROPATHOLOGICA COMMUNICATIONS, Vol: 2, ISSN: 2051-5960

Journal article

Kalaitzakis ME, Gentleman SM, Pearce RKB, 2013, Disturbed sleep in Parkinson's disease: anatomical and pathological correlates, NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol: 39, Pages: 644-653, ISSN: 0305-1846

Journal article

Williams MR, Marsh R, Macdonald CD, Jain J, Pearce RKB, Hirsch SR, Ansorge O, Gentleman SM, Maier Met al., 2013, Neuropathological changes in the nucleus basalis in schizophrenia, EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, Vol: 263, Pages: 485-495, ISSN: 0940-1334

Journal article

Williams MR, Harb H, Pearce RKB, Hirsch SR, Maier Met al., 2013, Oligodendrocyte density is changed in the basolateral amygdala in schizophrenia but not depression, SCHIZOPHRENIA RESEARCH, Vol: 147, Pages: 402-403, ISSN: 0920-9964

Journal article

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