A5062072066- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Neurological diseases and metabolism
- Neurological disorders and treatments
- Genetic Neurodegenerative Diseases
- Inflammatory Myopathies and Dermatomyositis
- Muscle Physiology and Disorders
- Amyotrophic Lateral Sclerosis Research
- Nuclear Receptors and Signaling
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Botulinum Toxin and Related Neurological Disorders
- Prion Diseases and Protein Misfolding
- Cellular transport and secretion
- Cerebrovascular and genetic disorders
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Neurogenetic and Muscular Disorders Research
- Lysosomal Storage Disorders Research
- Metabolism and Genetic Disorders
- Cardiomyopathy and Myosin Studies
- Glycogen Storage Diseases and Myoclonus
- Eosinophilic Disorders and Syndromes
- Hereditary Neurological Disorders
- RNA regulation and disease
- Neuroinflammation and Neurodegeneration Mechanisms
University College London
2016-2025
National Hospital for Neurology and Neurosurgery
2016-2025
Imperial College London
2014-2022
Hirosaki University
2022
Imperial College Healthcare NHS Trust
2022
St Mary's Hospital
2022
St. Mary's Hospital
2022
Medical Research Council
2015-2020
MRC Mitochondrial Biology Unit
2020
Great Ormond Street Hospital
2020
The clinical diagnosis of progressive supranuclear palsy (PSP) relies on the identification characteristic signs and symptoms. A proportion pathologically diagnosed cases do not develop these classic features, prove difficult to diagnose during life are considered as atypical PSP. aim this study was examine apparent dichotomy between typical PSP, compare biochemical genetic characteristics groups. In 103 consecutive confirmed we have identified two phenotypes by factor analysis which named...
Mutations in the glucocerebrosidase gene (GBA) are associated with Gaucher's disease, most common lysosomal storage disorder. Parkinsonism is an established feature of disease and increased frequency mutations GBA has been reported several different ethnic series sporadic Parkinson's disease. In this study, we evaluated British patients affected by We utilized DNA 790 257 controls, matched for age ethnicity, to screen within gene. Clinical data on all identified mutation carriers was...
The relative importance of Lewy- and Alzheimer-type pathologies to dementia in Parkinson's disease remains unclear. We have examined the combined associations α-synuclein, tau amyloid-β accumulation 56 pathologically confirmed cases, 29 whom had developed dementia. Cortical subcortical scores were obtained, while α-synuclein rated according respective Braak stages. Additionally, cortical Lewy body neurite determined densities generated using morphometry. Non-parametric statistics, together...
Multiple system atrophy (MSA) has varying clinical (MSA-P versus MSA-C) and pathological [striatonigral degeneration (SND) olivopontocerebellar (OPCA)] phenotypes. To investigate the spectrum of clinicopathological correlations, we performed a semi-quantitative analysis 100 MSA cases with well-characterized In 24 areas, chosen from both striatonigral (StrN) (OPC) regions, severity neuronal cell loss gliosis as well frequency glial (oligodendroglial) cytoplasmic inclusions (GCIs) (NCIs) were...
<b>Background:</b> Frontotemporal lobar degeneration (FTLD) is a genetically and pathologically heterogeneous neurodegenerative disorder. <b>Methods:</b> We collected blood samples from cohort of 225 patients with diagnosis within the FTLD spectrum examined heritability by giving each patient family history score, 1 (a clear autosomal dominant FTLD) through to 4 (no dementia). also looked for mutations in 5 disease-causing genes (<i>MAPT, GRN, VCP, CHMP2B</i>, <i>TARDP</i>) <i>FUS</i> gene,...
We have carried out a systematic review of the case files 242 donors with pathologically verified Parkinson's disease at Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity early clinical stages using data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343–8). Cases were segregated into earlier onset (25%), tremor dominant (31%), non-tremor (36%) rapid progression without...
We report a British family with young-onset Parkinson's disease (PD) and G51D SNCA mutation that segregates the disease. Family history was consistent autosomal dominant inheritance as both father sister of proband developed levodopa-responsive parkinsonism onset in their late thirties. Clinical features show similarity to those seen families triplication cases A53T mutation. Post-mortem brain examination revealed atrophy affecting frontal temporal lobes addition caudate, putamen, globus...
Prognostic predictors have not been defined for progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Subtypes of both disorders proposed on the basis early clinical features. We performed a retrospective chart review to investigate natural history pathologically confirmed cases PSP MSA. Survival data several clinically relevant milestones, namely: frequent falling, cognitive disability, unintelligible speech, severe dysphagia, dependence wheelchair mobility, use urinary...
Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants other lysosomal storage disorder genes is more broadly associated with disease susceptibility. The sequence kernel association test was used to interrogate variant among 54 genes, leveraging whole exome sequencing data from 1156 cases and 1679 control subjects. discovered significant rare, likely damaging risk....
To investigate the relationships between age, advanced clinical stages of Parkinson's disease and neuropathology, we surveyed 129 case records from donors with pathologically proven at Queen Square Brain Bank for Neurological Disorders. Cases were separated into five groups according to age death, thus comparing patients who reached stage different ages. Four milestones (frequent falls, visual hallucinations, dementia need residential care) occurred a similar time death in each group. There...
Abstract Clinical syndromes associated with progressive supranuclear palsy-tau pathology now include palsy-parkinsonism (PSP-P), in addition to classic Richardson's syndrome (RS) and pure akinesia gait freezing (PAGF). Although pathological heterogeneity of palsy (PSP) has also been established, attempts correlate this clinical findings have only rarely provided conclusive results. The aim study was investigate whether regional variations the types tau lesions or differences overall load may...
Significance Understanding loci nominated by genome-wide association studies (GWASs) is challenging. Here, we show, using the specific example of Parkinson disease, that identification protein–protein interactions can help determine most likely candidate for several GWAS loci. This result illustrates a significant general principle will apply across multiple diseases.
Relating clinical symptoms to neuroanatomical profiles of brain damage and ultimately tissue pathology is a key challenge in the field neurodegenerative disease particularly relevant heterogeneous disorders that comprise frontotemporal lobar degeneration spectrum. Here we present retrospective analysis clinical, neuropsychological neuroimaging (volumetric voxel-based morphometric) features pathologically ascertained cohort 95 cases classified according contemporary neuropathological...
Parkinson's disease is a common incurable neurodegenerative whose molecular aetiology remains unclear. The identification of Mendelian genes causing rare familial forms has revealed novel proteins and pathways that are likely to be relevant in the pathogenesis sporadic disease. Recently, mutations gene, PINK1, encoding 581 amino acid protein with both mitochondrial targeting serine/threonine kinase domains, were identified as cause autosomal recessive parkinsonism. This provided important...
Abstract To test whether the synucleinopathies Parkinson's disease and multiple system atrophy (MSA) share a common genetic etiology, we performed candidate single nucleotide polymorphism (SNP) association study of 384 most associated SNPs in genome‐wide 413 MSA cases 3,974 control subjects. The 10 significant were then replicated additional 108 537 controls. at SNCA locus significantly with risk for increased development (combined p = 5.5 × 12 ; odds ratio 6.2). Ann Neurol 2009;65:610–614
<h3>Importance</h3> Clinical subtyping of Parkinson disease at diagnosis is useful in estimating course and survival. Severity rate progression neuropathologies are important determinants clinical subtypes. <h3>Objective</h3> To provide longitudinal disease-course data neuropathologic correlation for newly proposed <h3>Design, Setting, Participants</h3> Retrospective cohort study consecutive patients with autopsy-confirmed who were regularly seen throughout their by hospital specialists the...