John Hardy

University College London, Londinium, England, United Kingdom

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Publications (586)5177.63 Total impact

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    ABSTRACT: We and others have described the neurodegenerative disorder caused by G51D SNCA mutation which shares characteristics of Parkinson's disease (PD) and multiple system atrophy (MSA). The objective of this investigation was to extend the description of the clinical and neuropathological hallmarks of G51D mutant SNCA-associated disease by the study of two additional cases from a further G51D SNCA kindred and to compare the features of this group with a SNCA duplication case and a H50Q SNCA mutation case. All three G51D patients were clinically characterised by parkinsonism, dementia, visual hallucinations, autonomic dysfunction and pyramidal signs with variable age at disease onset and levodopa response. The H50Q SNCA mutation case had a clinical picture that mimicked late-onset idiopathic PD with a good and sustained levodopa response. The SNCA duplication case presented with a clinical phenotype of frontotemporal dementia with marked behavioural changes, pyramidal signs, postural hypotension and transiently levodopa responsive parkinsonism. Detailed post-mortem neuropathological analysis was performed in all cases. All three G51D cases had abundant α-synuclein pathology with characteristics of both PD and MSA. These included widespread cortical and subcortical neuronal α-synuclein inclusions together with small numbers of inclusions resembling glial cytoplasmic inclusions (GCIs) in oligodendrocytes. In contrast the H50Q and SNCA duplication cases, had α-synuclein pathology resembling idiopathic PD without GCIs. Phosphorylated α-synuclein was present in all inclusions types in G51D cases but was more restricted in SNCA duplication and H50Q mutation. Inclusions were also immunoreactive for the 5G4 antibody indicating their highly aggregated and likely fibrillar state. Our characterisation of the clinical and neuropathological features of the present small series of G51D SNCA mutation cases should aid the recognition of this clinico-pathological entity. The neuropathological features of these cases consistently share characteristics of PD and MSA and are distinct from PD patients carrying the H50Q or SNCA duplication.
    Molecular Neurodegeneration 12/2015; 10(1). DOI:10.1186/s13024-015-0038-3 · 6.56 Impact Factor
  • Annals of Neurology 09/2015; DOI:10.1002/ana.24527 · 9.98 Impact Factor
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    ABSTRACT: Accurate diagnosis and early detection of complex diseases, such as Parkinson's disease, has the potential to be of great benefit for researchers and clinical practice. We aimed to create a non-invasive, accurate classification model for the diagnosis of Parkinson's disease, which could serve as a basis for future disease prediction studies in longitudinal cohorts. We developed a model for disease classification using data from the Parkinson's Progression Marker Initiative (PPMI) study for 367 patients with Parkinson's disease and phenotypically typical imaging data and 165 controls without neurological disease. Olfactory function, genetic risk, family history of Parkinson's disease, age, and gender were algorithmically selected by stepwise logistic regression as significant contributors to our classifying model. We then tested the model with data from 825 patients with Parkinson's disease and 261 controls from five independent cohorts with varying recruitment strategies and designs: the Parkinson's Disease Biomarkers Program (PDBP), the Parkinson's Associated Risk Study (PARS), 23andMe, the Longitudinal and Biomarker Study in PD (LABS-PD), and the Morris K Udall Parkinson's Disease Research Center of Excellence cohort (Penn-Udall). Additionally, we used our model to investigate patients who had imaging scans without evidence of dopaminergic deficit (SWEDD). In the population from PPMI, our initial model correctly distinguished patients with Parkinson's disease from controls at an area under the curve (AUC) of 0·923 (95% CI 0·900-0·946) with high sensitivity (0·834, 95% CI 0·711-0·883) and specificity (0·903, 95% CI 0·824-0·946) at its optimum AUC threshold (0·655). All Hosmer-Lemeshow simulations suggested that when parsed into random subgroups, the subgroup data matched that of the overall cohort. External validation showed good classification of Parkinson's disease, with AUCs of 0·894 (95% CI 0·867-0·921) in the PDBP cohort, 0·998 (0·992-1·000) in PARS, 0·955 (no 95% CI available) in 23andMe, 0·929 (0·896-0·962) in LABS-PD, and 0·939 (0·891-0·986) in the Penn-Udall cohort. Four of 17 SWEDD participants who our model classified as having Parkinson's disease converted to Parkinson's disease within 1 year, whereas only one of 38 SWEDD participants who were not classified as having Parkinson's disease underwent conversion (test of proportions, p=0·003). Our model provides a potential new approach to distinguish participants with Parkinson's disease from controls. If the model can also identify individuals with prodromal or preclinical Parkinson's disease in prospective cohorts, it could facilitate identification of biomarkers and interventions. National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Michael J Fox Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.
    The Lancet Neurology 08/2015; DOI:10.1016/S1474-4422(15)00178-7 · 21.90 Impact Factor
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    ABSTRACT: Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP) - an Alzheimer disease risk factor - although the possession of extra copies of other chromosome 21 genes may also play a part. Further study of the mechanisms underlying the development of Alzheimer disease in people with Down syndrome could provide insights into the mechanisms that cause dementia in the general population.
    Nature Reviews Neuroscience 08/2015; 16(9). DOI:10.1038/nrn3983 · 31.43 Impact Factor
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    ABSTRACT: Objective Dementia with Lewy bodies is an α-synucleinopathy characterized by neocortical Lewy-related pathology (LRP). We carried out a genome-wide association study (GWAS) on neocortical LRP in a population-based sample of subjects aged 85 or over.MethodsLRP was analyzed in 304 subjects in the Vantaa 85+ sample from Southern Finland. The GWAS included 41 cases with midbrain, hippocampal, and neocortical LRP and 177 controls without midbrain and hippocampal LRP. The Medical Research Council Cognitive Function and Ageing Study (CFAS) material was used for replication (51 cases and 131 controls).ResultsBy analyzing 327,010 markers the top signal was obtained at the HLA-DPA1/DPB1 locus (P = 1.29 × 10−7); five other loci on chromosomes 15q14, 2p21, 2q31, 18p11, and 5q23 were associated with neocortical LRP at P < 10−5. Two loci were marked by multiple markers, 2p21 (P = 3.9 × 10−6, upstream of the SPTBN1 gene), and HLA-DPA1/DPB1; these were tested in the CFAS material. Single marker (P = 0.0035) and haplotype (P = 0.04) associations on 2p21 were replicated in CFAS, whereas HLA-DPA1/DPB1 association was not. Bioinformatic analyses suggest functional effects for the HLA-DPA1/DPB1 markers as well as the 15q14 marker rs8037309.InterpretationWe identified suggestive novel risk factors for neocortical LRP. SPTBN1 is the candidate on 2p21, it encodes beta-spectrin, an α-synuclein binding protein and a component of Lewy bodies. The HLA-DPA1/DPB1 association suggests a role for antigen presentation or alternatively, cis-regulatory effects, one of the regulated neighboring genes identified here (vacuolar protein sorting 52) plays a role in vesicular trafficking and has been shown to interact with α-synuclein in a yeast model.
    08/2015; 2(9). DOI:10.1002/acn3.231
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    ABSTRACT: Myoclonus-dystonia (M-D) is a very rare movement disorder, caused in approximately 30-50% of cases by mutations in SGCE. The CACNA1B variant c.4166G>A; (p.R1389H) was recently reported as the likely causative mutation in a single 3-generation Dutch pedigree with 5 subjects affected by a unique dominant M-D syndrome and cardiac arrhythmias. In an attempt to replicate this finding, we assessed by direct sequencing the frequency of CACNA1B c.4166G>A; (p.R1389H) in a cohort of 520 M-D cases, in which SGCE mutations had been previously excluded. 146 cases (28%) had a positive family history of M-D. The frequency of the variant was also assessed in 489 neurologically healthy controls and in publicly available datasets of genetic variation (1000 Genomes, Exome Variant Server and Exome Aggregation Consortium). The variant was detected in a single sporadic case with M-D, but in none of the 146 probands with familial M-D. Overall, the variant was present at comparable frequencies in M-D cases (1/520; 0.19%) and healthy controls (1/489; 0.2%). A similar frequency of the variant was also reported in all publicly available databases. These results do not support a causal association between the CACNA1B c.4166G>A; (p.R1389H) variant and M-D. © The Author 2015. Published by Oxford University Press.
    Human Molecular Genetics 07/2015; 24(18). DOI:10.1093/hmg/ddv255 · 6.39 Impact Factor
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    ABSTRACT: Detecting and treating Alzheimer’s disease, before cognitive deficits occur, has become the health challenge of our time. The earliest known event in Alzheimer’s disease is rising Aβ. Previous studies have suggested that effects on synaptic transmission may precede plaque deposition. Here we report how relative levels of different soluble Aβ peptides in hippocampus, preceding plaque deposition, relate to synaptic and genomic changes. Immunoprecipitation-mass spectrometry was used to measured the early rise of different Aβ peptides in a mouse model of increasing Aβ (‘TASTPM’, transgenic for familial Alzheimer’s disease genes APP/PSEN1). In the third postnatal week, several Aβ peptides were above the limit of detection, including Aβ40, Aβ38 and Aβ42 with an intensity ratio of 6:3:2, respectively. By 2 months Aβ levels had only increased by 50% and, although the ratio of the different peptides remained constant, the first changes in synaptic currents, compared to WT mice could be detected with patch-clamp recordings. Between 2 and 4 months old, levels of Aβ40 rose by about seven-fold but Aβ42 rose by 25-fold, increasing Aβ42:Aβ40 ratio to 1:1. Only at 4 months did plaque deposition become detectable and only in some mice, however synaptic changes were evident in all hippocampal fields. These changes included increased glutamate release probability (P<0.001, n=7-9; consistent with the proposed physiological effect of Aβ) and loss of spontaneous action potential-mediated activity in the CA1 and dentate gyrus regions of the hippocampus (P<0.001, n=7). Hence synaptic changes occur when the Aβ levels and Aβ42:Aβ40 ratio are still low compared to those necessary for plaque deposition. Genome-wide microarray analysis revealed changes in gene expression at 2-4 months including synaptic genes being strongly affected but often showing significant changes only by 4 months. We thus demonstrate that, in a mouse model of rising Aβ, the initial deposition of plaques does not occur until several months after the first Aβ becomes detectable but coincides with a rapid acceleration in the rise of Aβ levels and the Aβ42:Aβ40 ratio. Prior to acceleration however, there is already a pronounced synaptic dysfunction, reflected as changes in synaptic transmission and altered gene expression, indicating that restoring synaptic function early in the disease progression may represent the earliest possible target for intervention in the onset of Alzheimer’s disease.
    Brain 07/2015; · 9.20 Impact Factor
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    ABSTRACT: The alternative splicing of the tau gene, MAPT, generates six protein isoforms in the adult human CNS. Tau splicing is developmentally regulated and dysregulated in disease. Mutations in MAPT that alter tau splicing cause frontotemporal dementia (FTD) with tau pathology, providing evidence for a causal link between altered tau splicing and disease. The use of induced pluripotent stem cell (iPSC) derived neurons has revolutionized the way we model neurological disease in vitro. However, as most tau mutations are located within or around the alternatively spliced exon 10, it is important that iPSC-neurons splice tau appropriately in order to be used as disease models. To address this issue, we analysed the expression, and splicing of tau in iPSC-derived cortical neurons from control patients and FTD patients with the 10+16 intronic mutation in MAPT. We show that control neurons only express the fetal tau isoform (0N3R), even at extended time points of 100 days in vitro. Neurons from FTD patients with the 10+16 mutation in MAPT express both 0N3R and 0N4R tau isoforms, demonstrating that this mutation overrides the developmental regulation of exon 10 inclusion in our in vitro model. Further, at extended time-points of 365 days in vitro, we observe a switch in tau splicing to include six tau isoforms as seen the adult human CNS. Our results demonstrate the importance of neuronal maturity for use in in vitro modeling and provide a system that will be important for understanding the functional consequences of altered tau splicing. © The Author 2015. Published by Oxford University Press.
    Human Molecular Genetics 07/2015; 24(18). DOI:10.1093/hmg/ddv246 · 6.39 Impact Factor
  • Stuart Pickering-Brown · John Hardy
    Brain 06/2015; DOI:10.1093/brain/awv173 · 9.20 Impact Factor
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    ABSTRACT: African-American (AA) individuals have a higher risk for late-onset Alzheimer's disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the Alzheimer's disease (AD)-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g., APOE, ABCA7), differed substantially from previous studies in EA. There likely are risk variants of higher frequency in AAs that have not been discovered. We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. Compared to controls, LOAD cases showed higher levels of African ancestry, both globally and at several LOAD relevant loci, which explained risk for AD beyond global differences. Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    Alzheimer's & dementia: the journal of the Alzheimer's Association 06/2015; DOI:10.1016/j.jalz.2015.02.012 · 12.41 Impact Factor
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    ABSTRACT: Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ∼10(-7) and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Neurobiology of aging 06/2015; 75(10). DOI:10.1016/j.neurobiolaging.2015.06.005 · 5.01 Impact Factor
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    ABSTRACT: The PLA2G6 gene encodes a group VIA calcium-independent phospholipase A2 beta enzyme that selectively hydrolyses glycerophospholipids to release free fatty acids. Mutations in PLA2G6 have been associated with disorders such as infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation type II and Karak syndrome. More recently, PLA2G6 was identified as the causative gene in a subgroup of patients with autosomal recessive early-onset dystonia-parkinsonism. Neuropathological examination revealed widespread Lewy body pathology and the accumulation of hyperphosphorylated tau, supporting a link between PLA2G6 mutations and parkinsonian disorders. Here we show that knockout of the Drosophila homologue of the PLA2G6 gene, iPLA2-VIA, results in reduced survival, locomotor deficits and organismal hypersensitivity to oxidative stress. Furthermore, we demonstrate that loss of iPLA2-VIA function leads to a number of mitochondrial abnormalities, including mitochondrial respiratory chain dysfunction, reduced ATP synthesis and abnormal mitochondrial morphology. Moreover, we show that loss of iPLA2-VIA is strongly associated with increased lipid peroxidation levels. We confirmed our findings using cultured fibroblasts taken from two patients with mutations in the PLA2G6 gene. Similar abnormalities were seen including elevated mitochondrial lipid peroxidation and mitochondrial membrane defects, as well as raised levels of cytoplasmic and mitochondrial reactive oxygen species. Finally, we demonstrated that deuterated polyunsaturated fatty acids, which inhibit lipid peroxidation, were able to partially rescue the locomotor abnormalities seen in aged flies lacking iPLA2-VIA gene function, and restore mitochondrial membrane potential in fibroblasts from patients with PLA2G6 mutations. Taken together, our findings demonstrate that loss of normal PLA2G6 gene activity leads to lipid peroxidation, mitochondrial dysfunction and subsequent mitochondrial membrane abnormalities. Furthermore we show that the iPLA2-VIA knockout fly model provides a useful platform for the further study of PLA2G6-associated neurodegeneration. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.
    Brain 05/2015; 138(7). DOI:10.1093/brain/awv132 · 9.20 Impact Factor
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    ABSTRACT: It is generally believed that splicing removes introns as single units from precursor messenger RNA transcripts. However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing. The extent to which recursive splicing occurs in other species and its mechanistic basis have not been examined. Here we identify highly conserved RS-sites in genes expressed in the mammalian brain that encode proteins functioning in neuronal development. Moreover, the RS-sites are found in some of the longest introns across vertebrates. We find that vertebrate recursive splicing requires initial definition of an 'RS-exon' that follows the RS-site. The RS-exon is then excluded from the dominant mRNA isoform owing to competition with a reconstituted 5' splice site formed at the RS-site after the first splicing step. Conversely, the RS-exon is included when preceded by cryptic promoters or exons that fail to reconstitute an efficient 5' splice site. Most RS-exons contain a premature stop codon such that their inclusion can decrease mRNA stability. Thus, by establishing a binary splicing switch, RS-sites demarcate different mRNA isoforms emerging from long genes by coupling cryptic elements with inclusion of RS-exons.
    Nature 05/2015; 521(7552). DOI:10.1038/nature14466 · 41.46 Impact Factor
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    Movement Disorders 05/2015; 30(7). DOI:10.1002/mds.26249 · 5.68 Impact Factor
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    ABSTRACT: Myoclonus-dystonia (M-D) is a rare movement disorder characterized by a combination of non-epileptic myoclonic jerks and dystonia. SGCE mutations represent a major cause for familial M-D being responsible for 30%-50% of cases. After excluding SGCE mutations, we identified through a combination of linkage analysis and whole-exome sequencing KCTD17 c.434 G>A p.(Arg145His) as the only segregating variant in a dominant British pedigree with seven subjects affected by M-D. A subsequent screening in a cohort of M-D cases without mutations in SGCE revealed the same KCTD17 variant in a German family. The clinical presentation of the KCTD17-mutated cases was distinct from the phenotype usually observed in M-D due to SGCE mutations. All cases initially presented with mild myoclonus affecting the upper limbs. Dystonia showed a progressive course, with increasing severity of symptoms and spreading from the cranio-cervical region to other sites. KCTD17 is abundantly expressed in all brain regions with the highest expression in the putamen. Weighted gene co-expression network analysis, based on mRNA expression profile of brain samples from neuropathologically healthy individuals, showed that KCTD17 is part of a putamen gene network, which is significantly enriched for dystonia genes. Functional annotation of the network showed an over-representation of genes involved in post-synaptic dopaminergic transmission. Functional studies in mutation bearing fibroblasts demonstrated abnormalities in endoplasmic reticulum-dependent calcium signaling. In conclusion, we demonstrate that the KCTD17 c.434 G>A p.(Arg145His) mutation causes autosomal dominant M-D. Further functional studies are warranted to further characterize the nature of KCTD17 contribution to the molecular pathogenesis of M-D. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    The American Journal of Human Genetics 05/2015; 96(6). DOI:10.1016/j.ajhg.2015.04.008 · 10.93 Impact Factor
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    ABSTRACT: Stroke is the second leading cause of death and the third leading cause of years of life lost. Genetic factors contribute to stroke prevalence, and candidate gene and genome-wide association studies (GWAS) have identified variants associated with ischemic stroke risk. These variants often have small effects without obvious biological significance. Exome sequencing may discover predicted protein-altering variants with a potentially large effect on ischemic stroke risk. To investigate the contribution of rare and common genetic variants to ischemic stroke risk by targeting the protein-coding regions of the human genome. The National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) analyzed approximately 6000 participants from numerous cohorts of European and African ancestry. For discovery, 365 cases of ischemic stroke (small-vessel and large-vessel subtypes) and 809 European ancestry controls were sequenced; for replication, 47 affected sibpairs concordant for stroke subtype and an African American case-control series were sequenced, with 1672 cases and 4509 European ancestry controls genotyped. The ESP's exome sequencing and genotyping started on January 1, 2010, and continued through June 30, 2012. Analyses were conducted on the full data set between July 12, 2012, and July 13, 2013. Discovery of new variants or genes contributing to ischemic stroke risk and subtype (primary analysis) and determination of support for protein-coding variants contributing to risk in previously published candidate genes (secondary analysis). We identified 2 novel genes associated with an increased risk of ischemic stroke: a protein-coding variant in PDE4DIP (rs1778155; odds ratio, 2.15; P = 2.63 × 10-8) with an intracellular signal transduction mechanism and in ACOT4 (rs35724886; odds ratio, 2.04; P = 1.24 × 10-7) with a fatty acid metabolism; confirmation of PDE4DIP was observed in affected sibpair families with large-vessel stroke subtype and in African Americans. Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke). Exome sequencing discovered 2 novel genes and mechanisms, PDE4DIP and ACOT4, associated with increased risk for ischemic stroke. In addition, ZFHX3 and ABCA1 were discovered to have protein-coding variants associated with ischemic stroke. These results suggest that genetic variation in novel pathways contributes to ischemic stroke risk and serves as a target for prediction, prevention, and therapy.
    05/2015; 72(7). DOI:10.1001/jamaneurol.2015.0582
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    ABSTRACT: Accumulation of Aβ peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimer's disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic Aβ peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by β-secretase and γ-secretase inhibition, as well as γ-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular Aβ signaling to neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Cell Reports 04/2015; 11(5). DOI:10.1016/j.celrep.2015.03.068 · 8.36 Impact Factor
  • Richard Killick · John Hardy · J. Paul Simons
    Biological psychiatry 04/2015; 77(8). DOI:10.1016/j.biopsych.2015.03.001 · 10.26 Impact Factor

Publication Stats

42k Citations
5,177.63 Total Impact Points


  • 2008–2015
    • University College London
      • Department of Molecular Neuroscience
      Londinium, England, United Kingdom
    • London Research Institute
      Londinium, England, United Kingdom
    • University of Miami Miller School of Medicine
      • Department of Psychiatry and Behavioral Sciences
      Miami, Florida, United States
  • 2007–2015
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
    • University of Miami
      كورال غيبلز، فلوريدا, Florida, United States
    • Duke University
      Durham, North Carolina, United States
  • 2011–2014
    • WWF United Kingdom
      Londinium, England, United Kingdom
  • 2013
    • University of Campinas
      Conceição de Campinas, São Paulo, Brazil
    • L'Institut du Cerveau et de la Moelle Épinière
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Cardiff University
      • School of Medicine
      Cardiff, Wales, United Kingdom
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
    • University of Thessaly
      • Κλινική Νευρολογίας
      Iolcus, Thessaly, Greece
    • Banner Alzheimer's Institute
      Phoenix, Arizona, United States
  • 2002–2011
    • National Institute on Aging
      • Laboratory of Neurogenetics (LNG)
      Baltimore, Maryland, United States
  • 2002–2009
    • National Institutes of Health
      • Laboratory of Neurogenetics
      Maryland, United States
  • 1992–2009
    • University of South Florida
      Tampa, Florida, United States
  • 2001–2008
    • University of Helsinki
      • Department of Pathology
      Helsinki, Uusimaa, Finland
    • University of Wales
      • College of Medicine
      Cardiff, Wales, United Kingdom
  • 2004
    • William Penn University
      Filadelfia, Pennsylvania, United States
    • Chang Gung University
      Hsin-chu-hsien, Taiwan, Taiwan
    • Hospital Universitario Fundacion Alcorcon
      Madrid, Madrid, Spain
  • 1997–2003
    • Mayo Foundation for Medical Education and Research
      • Department of Neurology
      Scottsdale, AZ, United States
  • 1996–2002
    • Washington University in St. Louis
      • Department of Psychiatry
      San Luis, Missouri, United States
  • 1998
    • Columbia University
      • Department of Neurology
      New York City, New York, United States
  • 1994
    • University of Essex
      Colchester, England, United Kingdom
  • 1989–1993
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 1991
    • University of Antwerp
      Antwerpen, Flanders, Belgium