Voyle, N;
Patel, H;
Folarin, A;
Newhouse, S;
Johnston, C;
Visser, PJ;
Dobson, RJB;
(2017)
Genetic Risk as a Marker of Amyloid-β and Tau Burden in Cerebrospinal Fluid.
Journal of Alzheimer's Disease
, 55
(4)
pp. 1417-1427.
10.3233/JAD-160707.
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Abstract
BACKGROUND: The search for a biomarker of Alzheimer’s disease (AD) pathology (amyloid- (A) and tau) is ongoing, with the best markers currently being measurements of A and tau in cerebrospinal fluid (CSF) and via positron emission tomography (PET) scanning. These methods are relatively invasive, costly, and often have high screening failure rates. Consequently, research is aiming to elucidate blood biomarkers of A and tau. OBJECTIVE: This study aims to investigate a case/control polygenic risk score (PGRS) as a marker of tau and investigate blood markers of a combined A and tau outcome for the first time. A sub-study also considers plasma tau as markers of A and tau pathology in CSF. METHODS: We used data from the EDAR*, DESCRIPA**, and Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts in a logistic regression analysis to investigate blood markers of A and tau in CSF. In particular, we investigated the extent to which a case/control PGRS is predictive of CSF tau, CSF amyloid, and a combined amyloid and tau outcome. The predictive ability of models was compared to that of age, gender, and APOE genotype (‘basic model’). RESULTS: In EDAR and DESCRIPA test data, inclusion of a case/control PGRS was no more predictive of A, and a combined A and tau endpoint than the basic models (accuracies of 66.0%, and 73.3% respectively). The tau model saw a small increase in accuracy compared to basic models (59.6%). ADNI 2 test data also showed a slight increase in accuracy for the A model when compared to the basic models (61.4%). CONCLUSION: We see some evidence that a case/control PGRS is marginally more predictive of A and tau pathology than the basic models. The search for predictive factors of A and tau pathologies, above and beyond demographic information, 1These aut
| Type: | Article |
|---|---|
| Title: | Genetic Risk as a Marker of Amyloid-β and Tau Burden in Cerebrospinal Fluid |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JAD-160707 |
| Publisher version: | http://doi.org/10.3233/JAD-160707 |
| Language: | English |
| Additional information: | © 2017 – IOS Press and the authors. All rights reserved This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0) |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Alzheimer's disease, biomarker, blood, multi-modal, polygenic risk score, tau, ALZHEIMERS-DISEASE, SWEDISH TWINS, BIOMARKERS, SCORE, PREDICTION, CRITERIA, LOCI |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1529797 |
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