Blood biomarkers for Alzheimer’s disease with the Lumipulse automated platform: Age-effect and clinical value interpretation

Abstract

Background

Advances in analytical methods have recently paved the way to Alzheimer’s disease (AD) biomarkers testing in blood along with the more established CSF testing. To ensure a forthcoming application of this low-invasive diagnostic that might allow to recognize early onset of dementia, appropriate pathological cut-points need to be defined.

Methods

In this cross-sectional study we measured blood and CSF neurofilament light chain (NFL), phosphorylated tau (pTau 181), Amyloid-β1-42 (AB 1–42) and Amyloid-β1-40 (AB 1–40) on a fully automated chemiluminescent platform (Lumipulse, Fujirebio) in 80 cognitively impaired patients and 55 cognitively unimpaired subjects. Clinical cut points were calculated with receiver-operator characteristic (ROC) curve analysis and a head-to-head comparison of blood and CSF testing was performed.

Results

Blood NFL best discriminant thresholds to distinguish neurodegenerative diseases from controls varied age-dependently, being 19 and 33 pg/mL in subjects 50–65 years and > 65 years respectively. AD was best framed by AB 1–42/1–40 ratio < 0.079 and ptau181 > 1 pg/mL. Though a strong correlation for all biomarkers, only blood AB ratio was equal to CSF testing for AD diagnosis.

Conclusions

The specific context of use might be considered to define the cut-offs of blood biomarkers of neurodegenerative diseases. Future efforts towards reference materials for each AD blood biomarker will improve clinical cut-offs.