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Alzheimer Disease: HELP
Articles by J. Hardy
Based on 8 articles published since 2010
(Why 8 articles?)
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Between 2010 and 2020, J. Hardy wrote the following 8 articles about Alzheimer Disease.
 
+ Citations + Abstracts
1 Review Alzheimer's disease. 2018

Lane, C A / Hardy, J / Schott, J M. ·Dementia Research Centre, UCL Institute of Neurology, London, UK. · Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. ·Eur J Neurol · Pubmed #28872215.

ABSTRACT: Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. In this review, current understanding of the epidemiology, genetics, pathology and pathogenesis of Alzheimer's disease is outlined, before its clinical presentation and current treatment strategies are discussed. Finally, the review discusses how our enhanced understanding of Alzheimer pathogenesis, including the recognition of a protracted preclinical phase, is informing new therapeutic strategies with the aim of moving from treatment to prevention.

2 Review Pathways to Alzheimer's disease. 2014

Hardy, J / Bogdanovic, N / Winblad, B / Portelius, E / Andreasen, N / Cedazo-Minguez, A / Zetterberg, H. · ·J Intern Med · Pubmed #24749173.

ABSTRACT: Recent trials of anti-amyloid agents have not produced convincing improvements in clinical outcome in Alzheimer's disease; however, the reason for these poor or inconclusive results remains unclear. Recent genetic data continue to support the amyloid hypothesis of Alzheimer's disease with protective variants being found in the amyloid gene and both common low-risk and rare high-risk variants for disease being discovered in genes that are part of the amyloid response pathways. These data support the view that genetic variability in how the brain responds to amyloid deposition is a potential therapeutic target for the disease, and are consistent with the notion that anti-amyloid therapies should be initiated early in the disease process.

3 Article Polygenic Risk Score Analysis of Alzheimer's Disease in Cases without APOE4 or APOE2 Alleles. 2019

Escott-Price, V / Myers, A / Huentelman, M / Shoai, M / Hardy, J. ·John Hardy, Department of Molecular Neuroscience and Reta Lilla Weston Laboratories, Institute of Neurology, London, UK, j.hardy@ucl.ac.uk. ·J Prev Alzheimers Dis · Pubmed #30569081.

ABSTRACT: The We and others have previously shown that polygenic risk score analysis (PRS) has considerable predictive utility for identifying those at high risk of developing Alzheimer's disease (AD) with an area under the curve (AUC) of >0.8. However, by far the greatest determinant of this risk is the apolipoprotein E locus with the E4 allele alone giving an AUC of ~0.68 and the inclusion of the protective E2 allele increasing this to ~0.69 in a clinical cohort. An important question is to determine how good PRS is at predicting risk in those who do not carry the E4 allele (E3 homozygotes, E3E2 and E2E2) and in those who carry neither the E4 or E2 allele (i.e. E3 homozygotes). Previous studies have shown that PRS remains a significant predictor of AD risk in clinical cohorts after controlling for APOE ε4 carrier status. In this study we assess the accuracy of PRS prediction in a cohort of pathologically confirmed AD cases and controls. The exclusion of APOE4 carriers has surprisingly little effect on the PRS prediction accuracy (AUC ~0.83 [95% CI: 0.80-0.86]), and the accuracy remained higher than that in clinical cohorts with APOE included as a predictor. From a practical perspective this suggests that PRS analysis will have predictive utility even in E4 negative individuals and may be useful in clinical trial design.

4 Article Whole-exome sequencing of the BDR cohort: evidence to support the role of the PILRA gene in Alzheimer's disease. 2018

Patel, T / Brookes, K J / Turton, J / Chaudhury, S / Guetta-Baranes, T / Guerreiro, R / Bras, J / Hernandez, D / Singleton, A / Francis, P T / Hardy, J / Morgan, K. ·Human Genetics Group, University of Nottingham, Nottingham, UK. · Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK. · UK Dementia Research Institute at UCL (UK DRI), London, UK. · Department of Medical Sciences, Institute of Biomedicine-iBiMED, University of Aveiro, Aveiro, Portugal. · Laboratory of Neurogenetics, National Institute of Aging, National Institute of Health, Bethesda, MD, USA. · Brains for Dementia Research Resource, Wolfson Centre for Age Related Diseases, King's College London, London, UK. ·Neuropathol Appl Neurobiol · Pubmed #29181857.

ABSTRACT: AIM: Late-onset Alzheimer's disease (LOAD) accounts for 95% of all Alzheimer's cases and is genetically complex in nature. Overlapping clinical and neuropathological features between AD, FTD and Parkinson's disease highlight the potential role of genetic pleiotropy across diseases. Recent genome-wide association studies (GWASs) have uncovered 20 new loci for AD risk; however, these exhibit small effect sizes. Using NGS, here we perform association analyses using exome-wide and candidate-gene-driven approaches. METHODS: Whole-exome sequencing was performed on 132 AD cases and 53 control samples. Exome-wide single-variant association and gene burden tests were performed for 76 640 nonsingleton variants. Samples were also screened for known causative mutations in familial genes in AD and other dementias. Single-variant association and burden analysis was also carried out on variants in known AD and other neurological dementia genes. RESULTS: Tentative single-variant and burden associations were seen in several genes with kinase and protease activity. Exome-wide burden analysis also revealed significant burden of variants in PILRA (P = 3.4 × 10 CONCLUSIONS: In addition, polygenic risk scores (PRS) were able to distinguish between cases and controls with 83.8% accuracy using 3268 variants, sex, age at death and APOE ε4 and ε2 status as predictors.

5 Article A novel Alzheimer disease locus located near the gene encoding tau protein. 2016

Jun, G / Ibrahim-Verbaas, C A / Vronskaya, M / Lambert, J-C / Chung, J / Naj, A C / Kunkle, B W / Wang, L-S / Bis, J C / Bellenguez, C / Harold, D / Lunetta, K L / Destefano, A L / Grenier-Boley, B / Sims, R / Beecham, G W / Smith, A V / Chouraki, V / Hamilton-Nelson, K L / Ikram, M A / Fievet, N / Denning, N / Martin, E R / Schmidt, H / Kamatani, Y / Dunstan, M L / Valladares, O / Laza, A R / Zelenika, D / Ramirez, A / Foroud, T M / Choi, S-H / Boland, A / Becker, T / Kukull, W A / van der Lee, S J / Pasquier, F / Cruchaga, C / Beekly, D / Fitzpatrick, A L / Hanon, O / Gill, M / Barber, R / Gudnason, V / Campion, D / Love, S / Bennett, D A / Amin, N / Berr, C / Tsolaki, Magda / Buxbaum, J D / Lopez, O L / Deramecourt, V / Fox, N C / Cantwell, L B / Tárraga, L / Dufouil, C / Hardy, J / Crane, P K / Eiriksdottir, G / Hannequin, D / Clarke, R / Evans, D / Mosley, T H / Letenneur, L / Brayne, C / Maier, W / De Jager, P / Emilsson, V / Dartigues, J-F / Hampel, H / Kamboh, M I / de Bruijn, R F A G / Tzourio, C / Pastor, P / Larson, E B / Rotter, J I / O'Donovan, M C / Montine, T J / Nalls, M A / Mead, S / Reiman, E M / Jonsson, P V / Holmes, C / St George-Hyslop, P H / Boada, M / Passmore, P / Wendland, J R / Schmidt, R / Morgan, K / Winslow, A R / Powell, J F / Carasquillo, M / Younkin, S G / Jakobsdóttir, J / Kauwe, J S K / Wilhelmsen, K C / Rujescu, D / Nöthen, M M / Hofman, A / Jones, L / Anonymous6731124 / Haines, J L / Psaty, B M / Van Broeckhoven, C / Holmans, P / Launer, L J / Mayeux, R / Lathrop, M / Goate, A M / Escott-Price, V / Seshadri, S / Pericak-Vance, M A / Amouyel, P / Williams, J / van Duijn, C M / Schellenberg, G D / Farrer, L A. ·Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA. · Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA. · Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. · Department of Epidemiology, Erasmus University Medical Center, Erasmus, Rotterdam,The Netherlands. · Department of Neurology, Erasmus University Medical Center, Erasmus, Rotterdam,The Netherlands. · Institute of Psychological Medicine and Clinical Neurosciences, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK. · Inserm U744, Lille, France. · Université Lille 2, Lille, France. · Institut Pasteur de Lille, Lille, France. · Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA. · Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA. · Trinity College, University of Dublin, Dublin, Ireland. · Macdonald Foundation Department of Human Genetics, University of Miami, Miami, FL, USA. · University of Iceland, Faculty of Medicine, Reykjavik, Iceland. · Icelandic Heart Association, Kopavogur, Iceland. · Department of Neurology, Boston University School of Medicine, Boston, MA, USA. · Netherlands Consortium for Healthy Aging, Leiden, The Netherlands. · Department of Radiology, Erasmus University Medical Center, Erasmus, Rotterdam,The Netherlands. · Institute for Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria. · Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, Riken, Kanagawa, Japan. · Foundation Jean Dausset-CEPH, Paris, France. · Memory Clinic of Fundació ACE, Institut Català de Neurociències Aplicades, Barcelona, Spain. · Centre National de Genotypage, Institut Genomique, Commissariat a l'energie Atomique, Evry, France. · Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany. · Institute of Human Genetics, University of Bonn, Bonn, Germany. · Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA. · German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. · Institute for Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany. · Department of Epidemiology, University of Washington, Seattle, WA, USA. · Centre National de Reference pour les Malades Alzheimer Jeunes (CNR-MAJ), Centre Hospitalier Régional Universitaire de Lille, Lille, France. · Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, MO, USA. · Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA. · National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA. · Departments of Health Services, University of Washington, Seattle, WA, USA. · Department of Geriatrics, University Paris Descartes, Sorbonne Paris V, France. · Geriatrics Department, Broca Hospital, Paris, France. · Mercer's Institute for Research on Aging, St James Hospital and Trinity College, Dublin, Ireland. · Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA. · CNR-MAJ, Inserm U1079, Rouen, France; University Hospital, 76031 Rouen, France. · University of Bristol Institute of Clinical Neurosciences, School of Clinical Sciences, Frenchay Hospital, Bristol, UK. · Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA. · Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA. · Inserm U888, Hôpital La Colombière, Montpellier, France. · Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece. · Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA. · Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA. · Departments of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA. · University of Pittsburgh Alzheimer's Disease Research Center, Pittsburgh, PA, USA. · Departments of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Dementia Research Centre, Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK. · Inserm U897, Victor Segalen University, F-33076, Bordeaux, France. · Department of Molecular Neuroscience, Institute of Neurology, London, UK. · Reta Lilla Weston Laboratories, Institute of Neurology, London, UK. · Department of Medicine, University of Washington, Seattle, WA, USA. · Oxford Healthy Aging Project (OHAP), Clinical Trial Service Unit, University of Oxford, Oxford, UK. · Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA. · Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson, MS, USA. · Institute of Public Health, University of Cambridge, Cambridge, UK. · Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology and Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. · Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA. · Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland. · Centre de Mémoire de Ressources et de Recherche de Bordeaux, CHU de Bordeaux, Bordeaux, France. · Department of Psychiatry, University of Frankfurt, Frankfurt am Main, Germany. · Department of Psychiatry, Ludwig Maximilians University, Munich, Germany. · Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA. · Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, University of Navarra School of Medicine, Pamplona, Spain. · CIBERNED, Instituto de Salud Carlos III, Madrid, Spain. · Group Health, Group Health Research Institute, Seattle, WA, USA. · Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA. · Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA. · Department of Pathology, University of Washington, Seattle, WA, USA. · Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, MD, USA. · Arizona Alzheimer's Consortium, Phoenix, AZ, USA. · Department of Psychiatry, University of Arizona, Phoenix, AZ, USA. · Banner Alzheimer's Institute, Phoenix, AZ, USA. · Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona. · Department of Geriatrics, Landspitali National University Hospital, Reykjavik, Iceland. · Division of Clinical Neurosciences, School of Medicine, University of Southampton, Southampton, UK. · Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, ON, Canada. · Cambridge Institute for Medical Research and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK. · Ageing Group, Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University, Belfast, UK. · PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, MA, USA. · Department of Neurology, Medical University of Graz, Graz, Austria. · Institute of Genetics, Queen's Medical Centre, University of Nottingham, Nottingham, UK. · King's College London, Institute of Psychiatry, Department of Neuroscience, De Crespigny Park, Denmark Hill, London, UK. · Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. · Department of Biology, Brigham Young University, Provo, Utah, USA. · Department of Genetics, University of North Carolina Chapel Hill, Chapel Hill, NC, USA. · Department of Psychiatry, Psychotherapy and Psychosomatics Martin-Luther-University Halle-Wittenberg, Halle, Germany. · Institute of Human Genetics, Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany. · Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA. · Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium. · Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. · Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD, USA. · Taub Institute on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA. · Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA. · Department of Neurology, Columbia University, New York, NY, USA. · McGill University and Génome Québec Innovation Centre, Montreal, QC, Canada. · University Hospital, CHRU Lille, Lille, France. · Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA. ·Mol Psychiatry · Pubmed #25778476.

ABSTRACT: APOE ɛ4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ɛ4+ (10 352 cases and 9207 controls) and APOE ɛ4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ɛ4 status. Suggestive associations (P<1 × 10(-4)) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ɛ4+: 1250 cases and 536 controls; APOE ɛ4-: 718 cases and 1699 controls). Among APOE ɛ4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10(-9)). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ɛ4+ subjects (CR1 and CLU) or APOE ɛ4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10(-7)) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P ⩽ 1.3 × 10(-8)), frontal cortex (P ⩽ 1.3 × 10(-9)) and temporal cortex (P⩽1.2 × 10(-11)). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10(-6)) and temporal cortex (P=2.6 × 10(-6)). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ɛ4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted.

6 Article Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. 2015

Desikan, R S / Schork, A J / Wang, Y / Witoelar, A / Sharma, M / McEvoy, L K / Holland, D / Brewer, J B / Chen, C-H / Thompson, W K / Harold, D / Williams, J / Owen, M J / O'Donovan, M C / Pericak-Vance, M A / Mayeux, R / Haines, J L / Farrer, L A / Schellenberg, G D / Heutink, P / Singleton, A B / Brice, A / Wood, N W / Hardy, J / Martinez, M / Choi, S H / DeStefano, A / Ikram, M A / Bis, J C / Smith, A / Fitzpatrick, A L / Launer, L / van Duijn, C / Seshadri, S / Ulstein, I D / Aarsland, D / Fladby, T / Djurovic, S / Hyman, B T / Snaedal, J / Stefansson, H / Stefansson, K / Gasser, T / Andreassen, O A / Dale, A M / Anonymous6381124. ·Department of Radiology, University of California, San Diego, La Jolla, CA, USA. · Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA. · Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA. · NORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. · Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research University of Tubingen, Tubingen, Germany. · Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany. · Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. · Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, UK. · The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA. · Department of Neurology, Taub Institute on Alzheimer's Disease and the Aging Brain, and Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA. · Department of Molecular Physiology and Biophysics, Vanderbilt Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA. · Departments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Biostatistics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA. · Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · German Center for Neurodegenerative Diseases (DZNE)-Tübingen, Paul-Ehrlich-Straße 15, Tübingen, Germany. · Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA. · Sorbonne Université, UPMC Univ Paris 06, Paris, France. · UCL Genetics Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. · Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. · INSERM UMR1043, CPTP, CHU Purpan, Toulouse, France. · Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA. · The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA. · Deparment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands. · Deparment of Internal Medicine, University of Washington, Seattle, WA, USA. · Icelandic Heart Association, Kopavogur, Iceland. · Department of Epidemiology, University of Washington, Seattle, WA, USA. · Laboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Washington, DC, USA. · Department of Neurology, Boston University School of Medicine, Boston, MA, USA. · Norwegian Centre for Dementia Research, Department of Old Age Psychiatry, Oslo University Hospital, Oslo, Norway. · Department of Geriatric Psychiatry, Akershus University Hospital, Oslo, Norway. · Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. · Alzheimer's Disease Research Centre, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden. · Institute of Clinical Medicine, University of Oslo, Oslo, Norway. · Department of Neurology, Akershus University Hospital, Oslo, Norway. · Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. · Department of Geriatric Medicine, University Hospital Reykjavik, Reykjavik, Iceland. · deCODE Genetics/Amgen, Reykjavik, Iceland. · Faculty of Medicine, University of Iceland, Reykjavik, Iceland. ·Mol Psychiatry · Pubmed #25687773.

ABSTRACT: We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.

7 Article Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease. 2013

Lambert, J C / Ibrahim-Verbaas, C A / Harold, D / Naj, A C / Sims, R / Bellenguez, C / DeStafano, A L / Bis, J C / Beecham, G W / Grenier-Boley, B / Russo, G / Thorton-Wells, T A / Jones, N / Smith, A V / Chouraki, V / Thomas, C / Ikram, M A / Zelenika, D / Vardarajan, B N / Kamatani, Y / Lin, C F / Gerrish, A / Schmidt, H / Kunkle, B / Dunstan, M L / Ruiz, A / Bihoreau, M T / Choi, S H / Reitz, C / Pasquier, F / Cruchaga, C / Craig, D / Amin, N / Berr, C / Lopez, O L / De Jager, P L / Deramecourt, V / Johnston, J A / Evans, D / Lovestone, S / Letenneur, L / Morón, F J / Rubinsztein, D C / Eiriksdottir, G / Sleegers, K / Goate, A M / Fiévet, N / Huentelman, M W / Gill, M / Brown, K / Kamboh, M I / Keller, L / Barberger-Gateau, P / McGuiness, B / Larson, E B / Green, R / Myers, A J / Dufouil, C / Todd, S / Wallon, D / Love, S / Rogaeva, E / Gallacher, J / St George-Hyslop, P / Clarimon, J / Lleo, A / Bayer, A / Tsuang, D W / Yu, L / Tsolaki, M / Bossù, P / Spalletta, G / Proitsi, P / Collinge, J / Sorbi, S / Sanchez-Garcia, F / Fox, N C / Hardy, J / Deniz Naranjo, M C / Bosco, P / Clarke, R / Brayne, C / Galimberti, D / Mancuso, M / Matthews, F / Anonymous4671124 / Anonymous4681124 / Anonymous4691124 / Anonymous4701124 / Moebus, S / Mecocci, P / Del Zompo, M / Maier, W / Hampel, H / Pilotto, A / Bullido, M / Panza, F / Caffarra, P / Nacmias, B / Gilbert, J R / Mayhaus, M / Lannefelt, L / Hakonarson, H / Pichler, S / Carrasquillo, M M / Ingelsson, M / Beekly, D / Alvarez, V / Zou, F / Valladares, O / Younkin, S G / Coto, E / Hamilton-Nelson, K L / Gu, W / Razquin, C / Pastor, P / Mateo, I / Owen, M J / Faber, K M / Jonsson, P V / Combarros, O / O'Donovan, M C / Cantwell, L B / Soininen, H / Blacker, D / Mead, S / Mosley, T H / Bennett, D A / Harris, T B / Fratiglioni, L / Holmes, C / de Bruijn, R F / Passmore, P / Montine, T J / Bettens, K / Rotter, J I / Brice, A / Morgan, K / Foroud, T M / Kukull, W A / Hannequin, D / Powell, J F / Nalls, M A / Ritchie, K / Lunetta, K L / Kauwe, J S / Boerwinkle, E / Riemenschneider, M / Boada, M / Hiltuenen, M / Martin, E R / Schmidt, R / Rujescu, D / Wang, L S / Dartigues, J F / Mayeux, R / Tzourio, C / Hofman, A / Nöthen, M M / Graff, C / Psaty, B M / Jones, L / Haines, J L / Holmans, P A / Lathrop, M / Pericak-Vance, M A / Launer, L J / Farrer, L A / van Duijn, C M / Van Broeckhoven, C / Moskvina, V / Seshadri, S / Williams, J / Schellenberg, G D / Amouyel, P. · ·Nat Genet · Pubmed #24162737.

ABSTRACT: Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

8 Minor CSF biomarkers for Alzheimer's pathology and the effect size of APOE ɛ4. 2014

Andreasson, U / Lautner, R / Schott, J M / Mattsson, N / Hansson, O / Herukka, S-K / Helisalmi, S / Ewers, M / Hampel, H / Wallin, A / Minthon, L / Hardy, J / Blennow, K / Zetterberg, H. ·Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden. · UCL Institute of Neurology, London, UK. · Clinical Memory Research Unit, Clinical Sciences Malmö, Lund University, Lund, Sweden. · Department of Neurology and Brain Research Unit, Clinical Research Centre/Mediteknia, University of Eastern Finland, Kuopio, Finland. · Institute for Stroke and Dementia Research (ISD), Ludwig-Maximilians-University, Munich, Germany. · Department of Psychiatry, Goethe University, Frankfurt, Germany. · 1] Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden [2] UCL Institute of Neurology, London, UK. ·Mol Psychiatry · Pubmed #23419830.

ABSTRACT: -- No abstract --