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. 2017;55(4):1417-1427.
doi: 10.3233/JAD-160707.

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

Nicola Voyle  1 , Hamel Patel  1 , Amos Folarin  1 , Stephen Newhouse  1 , Caroline Johnston  1 , Pieter Jelle Visser  2   3 , Richard J B Dobson  1   4   5 , Steven J Kiddle  1   6 ; EDAR and DESCRIPA study groups and the Alzheimer’s Disease Neuroimaging Initiative
Affiliations
Free PMC article

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

Nicola Voyle et al. J Alzheimers Dis. 2017.
Free PMC article

Abstract

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 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 Aβ, and a combined Aβ 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 Aβ model when compared to the basic models (61.4%).

Conclusion: We see some evidence that a case/control PGRS is marginally more predictive of Aβ and 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.*'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'.

Keywords: Alzheimer’s disease; biomarker; blood; multi-modal; polygenic risk score; tau.

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References

    1. Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, Dekosky ST, Gauthier S, Selkoe D, Bateman R, Cappa S, Crutch S, Engelborghs S, Frisoni GB, Fox NC, Galasko D, Habert MO, Jicha G a Nordberg A, Pasquier F, Rabinovici G, Robert P, Rowe C, Salloway S, Sarazin M, Epelbaum S, de Souza LC, Vellas B, Visser PJ, Schneider L, Stern Y, Scheltens P, Cummings JL (2014) Advancing research diagnostic criteria for Alzheimer’s disease: The IWG-2 criteria. Lancet Neurol 13, 614–629. - PubMed
    1. Hardy J, Higgins G (1992) Alzheimer’s disease: The amyloid cascade hypothesis. Science 256, 184–185. - PubMed
    1. Jack CR, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, Shaw LM, Vemuri P, Wiste HJ, Weigand SD, Lesnick TG, Pankratz VS, Donohue MC, Trojanowski JQ (2013) Tracking pathophysiological processes in Alzheimer’s disease: An updated hypothetical model of dynamic biomarkers. Lancet Neurol 12, 207–216. - PMC - PubMed
    1. Johnson KA, Minoshima S, Bohnen NI, Donohoe KJ, Foster NL, Herscovitch P, Karlawish JH, Rowe CC, Carrillo MC, Hartley DM, Hedrick S, Pappas V, Thies WH (2013) Appropriate use criteria for amyloid PET: A report of the Amyloid Imaging Task Force the Society of Nuclear Medicine and Molecular Imaging and the Alzheimer’s Association. Alzheimers Dement 9, E1–E16. - PMC - PubMed
    1. Buck AK, Herrmann K, Stargardt T, Dechow T, Krause BJ, Schreyögg J (2010) Economic evaluation of PET and PET/CT in oncology: Evidence and methodologic approaches. J Nucl Med Technol 38, 6–17. - PubMed

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