TY - JOUR
T1 - Genetic Risk as a Marker of Amyloid-ß and Tau Burden in Cerebrospinal Fluid
AU - Voyle, Nicola
AU - Patel, Hamel
AU - Folarin, Amos
AU - Newhouse, Stephen
AU - Johnston, Caroline
AU - Visser, Pieter Jelle
AU - Dobson, Richard J.B.
AU - Kiddle, Steven J.
AU - Tsolaki, Magda
AU - Wahlund, Lars Olof
AU - Yvonne-Freund-Levi, null
AU - Verhey, Frans
AU - Hausner, Lucrezia
AU - Johannsen, Gunhild Waldemar Peter
AU - Teunissen, Charlotte E.
AU - Vandenberghe, Rik
AU - Spiru, Luiza
AU - Wallin, Åsa K.
AU - Olde-Rikkert, Marcel
AU - EDAR and DESCRIPA study groups and the Alzheimer's Disease Neuroimaging Initiative
N1 - Publisher Copyright:
© 2017 - IOS Press and the authors. All rights reserved.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Background: The search for a biomarker of Alzheimer's disease (AD) pathology (amyloid-ß (Aß) and tau) is ongoing, with the best markers currently being measurements of Aß 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 Aß 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 Aß and tau outcome for the first time. A sub-study also considers plasma tau as markers of Aß 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 Aß 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 Aß, and a combined Aß 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 Aß model when compared to the basic models (61.4%). Conclusion: We see some evidence that a case/control PGRS is marginally more predictive of Aß and tau pathology than the basic models. The search for predictive factors of Aß and tau pathologies, above and beyond demographic information, is still ongoing. Better understanding of AD risk alleles, development of more sensitive assays, and studies of larger sample size are three avenues that may provide such factors. However, the clinical utility of possible predictors of brain Aß and tau pathologies must also be investigated. *'Beta amyloid oligomers in the early diagnosis of AD and as marker for treatment response' **'Development of screening guidelines and criteria for pre-dementia Alzheimer's disease'.
AB - Background: The search for a biomarker of Alzheimer's disease (AD) pathology (amyloid-ß (Aß) and tau) is ongoing, with the best markers currently being measurements of Aß 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 Aß 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 Aß and tau outcome for the first time. A sub-study also considers plasma tau as markers of Aß 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 Aß 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 Aß, and a combined Aß 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 Aß model when compared to the basic models (61.4%). Conclusion: We see some evidence that a case/control PGRS is marginally more predictive of Aß and tau pathology than the basic models. The search for predictive factors of Aß and tau pathologies, above and beyond demographic information, is still ongoing. Better understanding of AD risk alleles, development of more sensitive assays, and studies of larger sample size are three avenues that may provide such factors. However, the clinical utility of possible predictors of brain Aß and tau pathologies must also be investigated. *'Beta amyloid oligomers in the early diagnosis of AD and as marker for treatment response' **'Development of screening guidelines and criteria for pre-dementia Alzheimer's disease'.
KW - Alzheimer's disease
KW - biomarker
KW - blood
KW - multi-modal
KW - polygenic risk score
KW - tau
U2 - 10.3233/JAD-160707
DO - 10.3233/JAD-160707
M3 - Article
SN - 1387-2877
VL - 55
SP - 1417
EP - 1427
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 4
ER -