Non‐specific elevation of plasma phosphorylated tau181 during neurological illnesses affecting consciousness

Abstract

AbstractBackgroundPhosphorylated tau (p‐tau)181 has become a promising blood‐based biomarker for Alzheimer’s disease (AD), however, most prospective diagnostic studies excluded participants with other neurological illnesses. We studied the agreement of plasma p‐tau181 and cerebrospinal fluid (CSF) markers, according to AT(N) framework to evaluate the practicality of implementing blood‐based AD diagnosis.MethodPlasma and CSF were simultaneously collected in subjects presenting with alteration of consciousness to the King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Plasma p‐tau181 was measured using the single‐molecule array. CSF biomarkers were classified according to the AT(N) framework.ResultAmong 69 participants enrolled in the study, the median (IQR) age was 57 (28.5‐75) years, 32 (46.4%) were male, and 4 (5.8%) had AD. Plasma p‐tau181 yielded area under the curve (AUC) of 0.86, although its correlation with CSF p‐tau181 was relatively weak (Rho=0.42, p<0.001). Based on the Youden’s index, the optimal cut‐off point showed sensitivity, specificity, and overall agreement of 0.75, 0.85, and 0.84, respectively. Among subjects with negative CSF biomarkers of AD, plasma p‐tau181 was elevated beyond the usual cut‐offpoint derived from our memory clinic patients undergoing positron emission tomography in many, resulting in a poor specificity of 0.65.ConclusionPlasma p‐tau181 showed inadequate performance for diagnosing AD in patients with other neurological illnesses and warrant great caution if used.