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- O'Connor, A., et al.
(författare)
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Plasma phospho-tau181 in presymptomatic and symptomatic familial Alzheimer's disease: a longitudinal cohort study
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 5967-5976
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Tidskriftsartikel (refereegranskat)abstract
- Blood biomarkers have great potential to advance clinical care and accelerate trials in Alzheimer's disease (AD). Plasma phospho-tau181 (p-tau181) is a promising blood biomarker however, it is unknown if levels increase in presymptomatic AD. Therefore, we investigated the timing of p-tau181 changes using 153 blood samples from 70 individuals in a longitudinal study of familial AD (FAD). Plasma p-tau181 was measured, using an in-house single molecule array assay. We compared p-tau181 between symptomatic carriers, presymptomatic carriers, and non-carriers, adjusting for age and sex. We examined the relationship between p-tau181 and neurofilament light and estimated years to/from symptom onset (EYO), as well as years to/from actual onset in a symptomatic subgroup. In addition, we studied associations between p-tau181 and clinical severity, as well testing for differences between genetic subgroups. Twenty-four were presymptomatic carriers (mean baseline EYO -9.6 years) while 27 were non-carriers. Compared with non-carriers, plasma p-tau181 concentration was higher in both symptomatic (p < 0.001) and presymptomatic mutation carriers (p < 0.001). Plasma p-tau181 showed considerable intra-individual variability but individual values discriminated symptomatic (AUC 0.93 [95% CI 0.85-0.98]) and presymptomatic (EYO >= -7 years) (AUC 0.86 [95% CI 0.72-0.94]) carriers from non-carriers of the same age and sex. From a fitted model there was evidence (p = 0.050) that p-tau181 concentrations were higher in mutation carriers than non-carriers from 16 years prior to estimated symptom onset. Our finding that plasma p-tau181 concentration is increased in symptomatic and presymptomatic FAD suggests potential utility as an easily accessible biomarker of AD pathology.
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