Genetic risk as a marker of amyloid-beta and tau in cerebrospinal fluid

Nicola Joanne Voyle, Hamel Patel, Amos Folarin, Stephen Newhouse, Caroline Johnston, Pieter Jelle Visser, Richard James Butler Dobson, Steven John Kiddle, EDAR and DESCRIPA

Research output: Contribution to journalArticlepeer-review


BACKGROUND: The search for a biomarker of Alzheimer’s Disease (AD) pathology (amyloid-β (Aβ) and tau) is ongoing, with the best markers currently being measurements of Aβ and tau in the 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 Aβ 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 Aβ and tau outcome for the first time. A sub-study also considers plasma tau as markers of Aβ 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 Aβ 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 tau, Aβ and a combined Aβ and tau endpoint than the basic models (accuracies of 58.4%, 66.0% and 73.3% respectively). Similar results were seen in ADNI 2 test data.

CONCLUSION: We see that a case/control PGRS is no more predictive of Aβ or tau pathology than the basic models. The search for predictive factors of Aβ 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 Aβ and tau pathologies must also be investigated.
Original languageEnglish
Publication statusAccepted/In press - 29 Sept 2016


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