Predicting clinical decline and conversion to Alzheimer’s disease or dementia using novel Elecsys Aβ(1–42), pTau and tTau CSF immunoassays

Abstract

AbstractWe evaluated the performance of CSF biomarkers for predicting risk of clinical decline and conversion to dementia in non-demented patients with cognitive symptoms. CSF samples from patients in two multicentre longitudinal studies (ADNI, n = 619; BioFINDER, n = 431) were analysed. Aβ(1–42), tTau and pTau CSF concentrations were measured using Elecsys CSF immunoassays, and tTau/Aβ(1–42) and pTau/Aβ(1–42) ratios calculated. Patients were classified as biomarker (BM)-positive or BM-negative at baseline. Ability of biomarkers to predict risk of clinical decline and conversion to AD/dementia was assessed using pre-established cut-offs for Aβ(1–42) and ratios; tTau and pTau cut-offs were determined. BM-positive patients showed greater clinical decline than BM-negative patients, demonstrated by greater decreases in MMSE scores (all biomarkers: –2.10 to –0.70). Risk of conversion to AD/dementia was higher in BM-positive patients (HR: 1.67 to 11.48). Performance of Tau/Aβ(1–42) ratios was superior to single biomarkers, and consistent even when using cut-offs derived in a different cohort. Optimal pTau and tTau cut-offs were approximately 27 pg/mL and 300 pg/mL in both BioFINDER and ADNI. Elecsys pTau/Aβ(1–42) and tTau/Aβ(1–42) are robust biomarkers for predicting risk of clinical decline and conversion to dementia in non-demented patients, and may support AD diagnosis in clinical practice.