A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42 Kristel Sleegers,

Slides:

Advertisements

Similar presentations

Linkage and Association Studies Identify a Novel Locus for Alzheimer Disease at 7q36 in a Dutch Population-Based Sample Rosa Rademakers, Marc Cruts, Kristel.

Advertisements

2015 Alzheimer's disease facts and figures Alzheimer's & Dementia: The Journal of the Alzheimer's Association Volume 11, Issue 3, Pages (March.

Vladimir S. Fonov, Mahsa Dadar, Xiao Yiming, D. Louis Collins

Discriminatory and predictive capabilities of enzyme-linked immunosorbent assay and multiplex platforms in a longitudinal Alzheimer’s disease study Wesley.

Journal of the Neurological Sciences

Volume 3, Issue 1, Pages (January 2017)

Early pathologic amyloid induces hypersynchrony of BOLD resting-state networks in transgenic mice and provides an early therapeutic window before amyloid.

Mutation frequency of pathogenic genes in familial Alzheimer’s disease in China Jianping Jia, Liyong Wu, Wei Qin, Dan Li, Luxi Shen, Hanzhi Li, Qianqian.

Alzheimer's & Dementia: The Journal of the Alzheimer's Association

Alzheimer's & Dementia: The Journal of the Alzheimer's Association

INCREASED CSF LEVELS OF BIOMARKERS FOR NEURODEGENERATION IN FTLD-GRN MUTATION CARRIERS Joery Goossens, Sara Van Mossevelde, Tobi Van den Bossche, Anne.

Dement Geriatr Cogn Disord Extra 2014;4: DOI: /

Cerebrospinal fluid Aβ42 is the best predictor of clinical progression in patients with subjective complaints Argonde C. van Harten, Pieter Jelle Visser,

Christine Bredfeldt, Kristen Rice, Lisa Alecxih

Polygenic score prediction captures nearly all common genetic risk for Alzheimer's disease Valentina Escott-Price, Maryam Shoai, Richard Pither, Julie.

Volume 5, Pages (December 2016)

Alzheimer's & Dementia: The Journal of the Alzheimer's Association

Plasma nutrient status of patients with Alzheimer's disease: Systematic review and meta-analysis Sofia Lopes da Silva, Bruno Vellas, Saskia Elemans,

Alzheimer’s disease core biomarkers and prediction of dementia in MCI: The effect of age at onset Anna Caroli, Samantha Galluzzi, Clarissa Ferrari, Annapaola.

An amylin analog used as a challenge test for Alzheimer's disease

Recommendations for cerebrospinal fluid Alzheimer's disease biomarkers in the diagnostic evaluation of mild cognitive impairment Sanna-Kaisa Herukka,

Colin Groot, Chris W. J. van der Weijden, Wiesje M

Volume 2, Issue 1, Pages (January 2016)

Duc T.M. Nguyen, Edward A. Graviss

Early diagnosis of mild cognitive impairment and Alzheimer's disease based on salivary lactoferrin Eva Carro, Fernando Bartolomé, Félix Bermejo-Pareja,

All-Cause and Cause-Specific Mortality in Patients with Psoriasis in Taiwan: A Nationwide Population-Based Study Meng-Sui Lee, Yi-Chun Yeh, Yun-Ting.

Cerebrospinal fluid apolipoprotein E concentration decreases after seizure Liang Wang, Yanbing Han, Dan Chen, Zheng Xiao, Zhiqin Xi, Fei Xiao, Xuefeng.

Prediction rule for cardiovascular events and mortality in peripheral arterial disease patients: Data from the prospective Second Manifestations of ARTerial.

Tariq Shafi, Andrew S. Levey Advances in Chronic Kidney Disease

When fasted is not empty: a retrospective cohort study of gastric content in fasted surgical patients† P Van de Putte, L Vernieuwe, A Jerjir, L Verschueren,

Plasma nutrient status of patients with Alzheimer's disease: Systematic review and meta-analysis Sofia Lopes da Silva, Bruno Vellas, Saskia Elemans,

An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers R. van der Schrier, K. Jonkman, M. van Velzen,

Evidence for Sex-Specific Risk Alleles in Autism Spectrum Disorder

Sabina Hunziker, MD, MPH, Jennifer Stevens, MD, MS, Michael D

Volume growth of abdominal aortic aneurysms correlates with baseline volume and increasing finite element analysis-derived rupture risk Moritz Lindquist.

Intraoperative hypotension and delirium after on-pump cardiac surgery†

Comparison of EuroSCORE II, Original EuroSCORE, and The Society of Thoracic Surgeons Risk Score in Cardiac Surgery Patients Niv Ad, MD, Sari D. Holmes,

Christine W. Duarte, PhD, Adam W. Black, Kimberly Murray, Amy E

Figure 2 Association between coronary artery disease polygenic risk score and the presence of migraine Results are given as odds ratios with 95% confidence.

Hypotension during induction of anaesthesia is neither a reliable nor a useful quality measure for comparison of anaesthetists’ performance R.H. Epstein,

A Risk Prediction Model for Invasive Fungal Disease in Critically Ill Patients in the Intensive Care Unit Fangyi Li, Minggen Zhou, Zijun Zou, Weichao.

Erratum Regarding “Ultrasound Monitoring to Detect Access Stenosis in Hemodialysis Patients: A Systematic Review” (Am J Kidney Dis. 2008;51(4): )

Figure 1 3D heat maps generated by GBM

Comparison of a Vascular Study Group of New England risk prediction model with established risk prediction models of in-hospital mortality after elective.

Volume 92, Issue 1, Pages (July 2017)

Tharick A. Pascoal, Sulantha Mathotaarachchi, Monica Shin, Andrea L

A systematic review and meta-analysis of abdominal compartment syndrome after endovascular repair of ruptured abdominal aortic aneurysms Christos D.

Prevalence and incidence of clinically diagnosed Alzheimer's disease dementia from 1994 to 2012 in a population study Kumar B. Rajan, Jennifer Weuve,

Bara Erhayiem, Rajpal Dhingsa, Christopher J

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries British Journal of Anaesthesia

Allen D. Roses, Michael W. Lutz, Ann M

Clifford R. Jack, Heather J. Wiste, Stephen D. Weigand, Terry M

Jeremy M. Silverman, Christopher J. Smith, Deborah B

The Reply The American Journal of Medicine

Prevalence and incidence of clinically diagnosed Alzheimer's disease dementia from 1994 to 2012 in a population study Kumar B. Rajan, Jennifer Weuve,

Assessing fitness for surgery: a comparison of questionnaire, incremental shuttle walk, and cardiopulmonary exercise testing in general surgical patients†

Ruth H. Keogh, Sanja Stanojevic Journal of Cystic Fibrosis

[18F]flutemetamol amyloid positron emission tomography in preclinical and symptomatic Alzheimer's disease: Specific detection of advanced phases of amyloid-β.

Longitudinal uncoupling of cerebral perfusion, glucose metabolism, and tau deposition in Alzheimer's disease Antoine Leuzy, Elena Rodriguez-Vieitez,

Figure 2 Correlation between wGRS and age at onset The figure shows the correlation between weighted genetic risk score (wGRS) and age at onset in all.

An externally validated robust risk predictive model of adverse outcomes after carotid endarterectomy Mohammad H. Eslami, MD, Denis Rybin, MS, Gheorghe.

Massimo S. Fiandaca, Mark E. Mapstone, Amrita K. Cheema, Howard J

Alzheimer's & Dementia: The Journal of the Alzheimer's Association

GREY MATTER CONNECTIVITY IS ASSOCIATED WITH CLINICAL PROGRESSION IN NON-DEMENTED, AMYLOID POSITIVE PATIENTS Betty M. Tijms, Mara ten Kate, Sander C.J.

Cerebral hypoperfusion is not associated with an increase in amyloid β pathology in middle-aged or elderly people Oskar Hansson, Sebastian Palmqvist,

Intersite variability of CSF Alzheimer’s disease biomarkers in clinical setting Julien Dumurgier, Olivier Vercruysse, Claire Paquet, Stéphanie Bombois,

The Gene Encoding Nicastrin, a Major γ-Secretase Component, Modifies Risk for Familial Early-Onset Alzheimer Disease in a Dutch Population-Based Sample

Suzanne E. Schindler, Julia D. Gray, Brian A

Increased risk for dementia both before and after stroke: A population-based study in women followed over 44 years Xinxin Guo, Svante Östling, Silke.

CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER.

Presentation transcript:

A 22-single nucleotide polymorphism Alzheimer's disease risk score correlates with family history, onset age, and cerebrospinal fluid Aβ42 Kristel Sleegers, Karolien Bettens, Arne De Roeck, Caroline Van Cauwenberghe, Elise Cuyvers, Jan Verheijen, Hanne Struyfs, Jasper Van Dongen, Steven Vermeulen, Sebastiaan Engelborghs, Mathieu Vandenbulcke, Rik Vandenberghe, Peter Paul De Deyn, Christine Van Broeckhoven Alzheimer's & Dementia: The Journal of the Alzheimer's Association Volume 11, Issue 12, Pages 1452-1460 (December 2015) DOI: 10.1016/j.jalz.2015.02.013 Copyright © 2015 The Authors Terms and Conditions

Fig. 1 Comparison of the discriminative ability of different models of GRS for AD. (A) Receiver operating characteristic (ROC) curves for the six GRS models detailed in Table 1, based on the AD and control cohort. Area under the curve (AUC) for APOE-S: 0.65, APOE-A: 0.67; ALL-WA: 0.70; ALL-WS: 0.68; ALL-C: 0.60, and OTH-W: 0.58. (B) Odds ratios (OR) of AD are presented with 95% confidence intervals (CI) for each quantile of ModelALL-WA, with the third (20% average GRS) quantile as reference. The x-axis gives numbers for increasing quantiles. *denotes a P value of <1.0e−15 based on Cochran-Armitage test for trend. Abbreviations: GRS, genetic risk score; AD, Alzheimer's disease; wGRS, weighted genetic risk score. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2015 11, 1452-1460DOI: (10.1016/j.jalz.2015.02.013) Copyright © 2015 The Authors Terms and Conditions

Fig. 2 GRS and family history of AD. (A) ROC curves for familial AD (FAD) patients (defined by at least one first degree relative with dementia, n = 206) versus controls and sporadic AD (SAD) patients (n = 899) versus controls. ROC curves for FAD based on ModelALL-WA (black curve; AUC = 0.78) and ModelAPOE-A (green curve; AUC = 0.76); ROC curves for SAD based on ModelALL-WA (red; AUC = 0.68) and ModelAPOE-A (blue; AUCAPOE = 0.65). (B) The percentage of familial AD (blue, n = 206), sporadic AD patients (red, n = 899), and control subjects (green, n = 1019) is shown per quantile. **denotes a P value of <1.0e−15 based on Cochran-Armitage test for trend when comparing FAD to SAD patients; *OR, 2.03 (95% CI, 1.27–3.27; P, .004) for positive family history of AD when comparing the upper fifth with the center fifth. Abbreviations: GRS, genetic risk score; AD, Alzheimer's disease; ROC, receiver operating characteristic; AUC, area under the curve; OR, odds ratio; CI, confidence interval. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2015 11, 1452-1460DOI: (10.1016/j.jalz.2015.02.013) Copyright © 2015 The Authors Terms and Conditions

Fig. 3 Negative correlation between GRS and onset age in patients. Scatterplot of onset age (y-axis) and GRS (x-axis). A regression line is presented with 95% CI. The association between onset age and GRS was determined using ModelALL-WS without incorporated age weights. Abbreviations: GRS, genetic risk score; CI, confidence interval. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2015 11, 1452-1460DOI: (10.1016/j.jalz.2015.02.013) Copyright © 2015 The Authors Terms and Conditions

Fig. 4 GRS-CSF biomarker correlations. Scatterplots of GRS ModelALL-WA with patient CSF concentrations of (A) Aβ1–42, (B) T-tau, and (C) P-tau181P. Regression lines are presented with 95% CI. Abbreviations: GRS, genetic risk score; CSF, cerebrospinal fluid; CI, confidence interval. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2015 11, 1452-1460DOI: (10.1016/j.jalz.2015.02.013) Copyright © 2015 The Authors Terms and Conditions

Supplementary Figure S1 Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2015 11, 1452-1460DOI: (10.1016/j.jalz.2015.02.013) Copyright © 2015 The Authors Terms and Conditions

Supplementary Figure S2 Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2015 11, 1452-1460DOI: (10.1016/j.jalz.2015.02.013) Copyright © 2015 The Authors Terms and Conditions

Supplementary Figure S3 Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2015 11, 1452-1460DOI: (10.1016/j.jalz.2015.02.013) Copyright © 2015 The Authors Terms and Conditions