Abstract
Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73–0.87] and 0.92 [95% CI 0.89–0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS.
Highlights
Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology with high accuracy in the general population
We and others have described the usefulness of cerebrospinal fluid (CSF) and amyloid positron emission tomography (PET) biomarkers to detect the core neuropathological hallmarks of AD in this population[5,6,7,8]
As previously reported[4,7], participants with Down syndrome (DS) and prodromal AD and AD dementia showed a decrease in the CSF ratio of Aβ1-42/1-40 and an increase in CSF concentration of total tau, p-tau[181] and NfL, as well as an increase in plasma concentration of NfL compared with asymptomatic subjects and euploid controls (Table 1)
Summary
Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology with high accuracy in the general population. We and others have described the usefulness of cerebrospinal fluid (CSF) and amyloid positron emission tomography (PET) biomarkers to detect the core neuropathological hallmarks of AD in this population[5,6,7,8] All these studies support the notion that AD in DS recapitulates the pattern observed in both sporadic and autosomal-dominant AD. The method lacked analytical sensitivity to measure plasma p-tau in around half of DS cases, and that study did not assess the AD clinical status or the diagnostic performance of this biomarker In this cross-sectional study, we assessed the accuracy of ptau[181] in plasma to detect AD in a large cohort of adults with DS and describe the association with other biochemical and neuroimaging AD biomarkers
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