Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function

Objectives Plasma P-tau181 is an increasingly established diagnostic marker for Alzheimer’s disease (AD). Further validation in prospective cohorts is still needed, as well as the study of confounding factors that could influence its blood level. Methods This study is ancillary to the prospective multicenter BALTAZAR cohort that enrolled participants with mild cognitive impairment (MCI) who were examined for conversion to dementia for up to three years. Plasma Ptau-181 was measured using the ultrasensitive Quanterix HD-X assay. Results Among 476 MCI participants, 67% were Aβ+ at baseline and 30% developed dementia. Plasma P-tau181 was higher in the Aβ+ population (3.9 [SD 1.4] vs. 2.6 [SD 1.4] pg/mL) and in MCI that converted to dementia (3.8 [SD 1.5] vs. 2.9 [SD 1.4] pg/mL). The addition of plasma P-tau181 to a logistic regression model combining age, sex, APOEε4 status and mini mental state examination (MMSE) improved predictive performance (AUC 0.691 to 0.744 for conversion and 0.786 to 0.849 for Aβ+). The Kaplan–Meier curve of conversion to dementia, according to the tertiles of plasma P-tau181, revealed a significant predictive value (Log rank P<.0001) with a hazard ratio of 3.8 [95%CI=2.5-5.8]. In addition, patients with plasma P-Tau(181) ≤2.32 pg/mL had a conversion rate of less than 20% over a 3-year period. Using a linear regression approach, chronic kidney disease (CKD), creatinine and glomerular filtration rate (eGFR) were independently associated with plasma P-tau181 concentrations. Conclusions Plasma P-tau181 effectively detects Aβ+ status and conversion to dementia, confirming the value of this blood biomarker for the management of AD. However, renal function significantly modifies its levels and may thus induce diagnostic errors if not taken into account. What is already known on this topic The clinical use of plasma phosphorylated tau 181 (P-tau181) for Alzheimer’s disease is being considered but further validation and study of confounding factors are still needed. What this study adds In our large prospective cohort, P-tau181 predicts brain amyloidopathy and conversion to dementia in patients with mild cognitive impairment, but renal function significantly alters plasma levels and thus may induce diagnostic errors if not taken into account. How this study might affect research, practice or policy Our study suggests that measurement of creatinine or estimation of glomerular filtration rate, which are easy and standardizable ways to provide information on renal function, will contribute to optimal interpretation of plasma P-tau181 results in routine clinical practice.