Elevation of plasma phosphorylated tau181 during neurological illnesses affecting consciousness and kidney dysfunction

Abstract

Introduction Phosphorylated tau (p‐tau)181 has become a promising blood‐based Alzheimer's disease (AD) biomarker. We studied the agreement of plasma p‐tau181 and cerebrospinal fluid (CSF) markers in patients with alteration of consciousness (AOC). Methods Plasma and CSF were simultaneously collected in participants presenting with AOC. Plasma p‐tau181 was measured using the single‐molecule array. CSF biomarkers were classified according to the amyloid/tau/neurodegeneration (AT[N]) framework. Results Among participants enrolled, the median (interquartile range) age was 57 (28.5–75) years and 5.8% had AD. Plasma p‐tau181 yielded area under the curve of 0.85 and showed moderate correlation with CSF p‐tau181 (Rho = 0.42, P < .001). Using the historical cut‐point, many non‐AD participants had elevated plasma p‐tau181 resulting in a specificity of 0.57. Plasma p‐tau181 correlated with the glomerular filtration rate (Rho = –0.52, P < .001). Among A− participants with elevated plasma p‐tau181, 42% had kidney dysfunction. Discussion Plasma p‐tau181 showed inadequate specificity in patients with AOC partially attributable to concomitant kidney dysfunction.

Predicting amyloid PET positivity using plasma p‐tau181 and other blood‐based biomarkers

“…In previous studies, including a study that analyzed the effect of p‐tau181 in a multi‐ethnic population, information on Asians was lacking 37 . Recently, the efficacy of blood‐based biomarkers in predicting amyloid positivity, hippocampal atrophy and future cognitive stage transition in the Asian population has been reported 29,38,39 . However, it is still unclear how p‐tau181 differs between ethnicities and validating the discriminative value of p‐tau181 in a single ethnicity is also important.…”

“…37 Recently, the efficacy of blood-based biomarkers in predicting amyloid positivity, hippocampal atrophy and future cognitive stage transition in the Asian population has been reported. 29,38,39 However, it is still unclear how p-tau181 differs between ethnicities and validating the discriminative value of p-tau181 in a single ethnicity is also important. Second, a limited number of amyloid PET participants (41 in the MCI group and 23 in the dementia group) were analyzed in the current study.…”