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

Abstract

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 multicentre Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk cohort that enrolled participants with mild cognitive impairment (MCI) who were examined for conversion to dementia for up to 3 years. Plasma Ptau-181 was measured using the ultrasensitive Quanterix HD-X assay.

Results: Among 476 MCI participants, 67% were amyloid positive (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 improved predictive performance (areas under the curve 0.691-0.744 for conversion and 0.786-0.849 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<0.0001) with an HR of 3.8 (95% CI 2.5 to 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, creatinine and estimated glomerular filtration rate 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.

Trial registration: ClinicalTrials.gov NCT01315639.

Keywords: alzheimer's disease; biochemistry; dementia.