Predicting clinical decline and conversion to Alzheimer's disease or dementia using novel Elecsys A?(1-42), pTau and tTau CSF immunoassays.

ABSTRACT: We 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. A?(1-42), tTau and pTau CSF concentrations were measured using Elecsys CSF immunoassays, and tTau/A?(1-42) and pTau/A?(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 A?(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/A?(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/A?(1-42) and tTau/A?(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.

SUBMITTER: Blennow K 

PROVIDER: S-EPMC6911086 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature