Genetic Risk as a Marker of Amyloid-? and Tau Burden in Cerebrospinal Fluid.

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, 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 A? 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'.

SUBMITTER: Voyle N 

PROVIDER: S-EPMC5181674 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature