Levels of cerebrospinal fluid biomarkers total tau and phosphorylated tau do not predict survival time after diagnosis of Alzheimer’s disease – An 18-year follow-up

Abstract

Background: The pathological process in Alzheimer’s disease (AD) probably starts decades before the onset of symptoms and the clinical AD diagnosis. In patients with AD, the level of cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ42) is usually lower, and the levels of total tau (T-tau) and phosphorylated tau (P-tau) higher than in healthy elderly people. However, the cutoffs differ between studies and the predictive values are too low to diagnose AD using only CSF biomarkers. Several previous reports have shown that the levels of T-tau and P-tau become pathological later in the course of AD compared with Aβ42, yet it is unclear if higher levels of tau shorten the individuals’ life expectancy after diagnosis. The current study aims to investigate whether pathological levels of T-tau and/or P-tau can predict survival in AD. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for the longitudinal assessment of cholinesterase inhibitor treatment in a routine clinical setting. This presentation includes all 151 participants clinically diagnosed with AD, who underwent a lumbar puncture. Patients were evaluated regarding cognitive and functional abilities at baseline (time of diagnosis) and semi-annually over 3 years. Socio-demographic characteristics, concomitant medications and the date of death were recorded. CSF was collected in polypropylene tubes, stored at −80 °C and analyzed after the clinical follow-up of the study was completed. The levels of T-tau, P-tau phosphorylated at Thr181 and Aβ42 were determined using xMAP technology. Pathological levels of CSF biomarkers were defined as: T-tau >100 ng/ml, P-tau >51 ng/ml and Aβ42 =126 and >=129 ng/ml) and P-tau (>=65 and >=70 ng/ml), respectively, were also examined; their lifespan did not differ from the other individuals. The actual continuous values of the CSF biomarkers or dichotomously coded normal/pathological, respectively, were not significant in Cox regression models adjusted for the above-mentioned predictors. Conclusion: Mortality in AD is complex and depends on many factors e.g., demographic and clinical. In this clinical-practice-based long-term study, almost half of the participants with AD had normal levels of tau. We found no clear results that the levels of T-tau and/or P-tau affect survival after diagnosis in AD. This observation does not support the theory that these patients have a more advanced disease. However, the individuals with pathological levels of tau had fewer years of education and worse cognitive status indicating a lower cognitive reserve capacity, which might influence life expectancy. These findings might be useful when considering new diagnostic criteria and when interpreting outcomes from future clinical trials of potentially disease-modifying AD therapies. (Less)