Crosswalk study on blood collection‐tube types for Alzheimer's disease biomarkers

Introduction Blood‐based Alzheimer's disease (AD) biomarkers show promise, but pre‐analytical protocol differences may pose problems. We examined seven AD blood biomarkers (amyloid beta [Aβ]42${\rm{A\beta }}]{_{42}}$, Aβ40${\rm{A}}{{{\beta}}_{40}}$, phosphorylatedtau[p−tau181${\rm{phosphorylated\;tau\;[p - ta}}{{\rm{u}}_{181}}$, total tau [t‐tau], neurofilament light chain [NfL], Aβ4240,${\rm{A}}{{{\beta}}_{\frac{{42}}{{40}}},$ and p−tau181Aβ42$\frac{{{\rm{p - ta}}{{\rm{u}}_{181}}}{{{\rm{A}}{{{\beta}}_{42}}}$) in three collection tube types (ethylenediaminetetraacetic acid [EDTA] plasma, heparin plasma, serum). Methods Plasma and serum were obtained from cerebrospinal fluid or amyloid positron emission tomography‐positive and ‐negative participants (N = 38) in the Wisconsin Registry for Alzheimer's Prevention. We modeled AD biomarker values observed in EDTA plasma versus heparin plasma and serum, and assessed correspondence with brain amyloidosis. Results Results suggested bias due to tube type, but crosswalks are possible for some analytes, with excellent model fit for NfL (R2${{\rm{R}}^2}\;$= 0.94), adequate for amyloid (R2${{\rm{R}}^2}\;$= 0.40‐0.69), and weaker for t‐tau (R2${{\rm{R}}^2}\;$= 0.04‐0.42) and p−tau181${\rm{p - ta}}{{\rm{u}}_{181}}$ ( R2${{\rm{R}}^2}\;$= 0.22‐0.29). Brain amyloidosis differentiated several measures, especially EDTA plasma pTau181Aβ42$\frac{{{\rm{pTa}}{{\rm{u}}_{181}}}{{{\rm{A}}{\beta _{42}}}$ (d$d\;$= 1.29). Discussion AD biomarker concentrations vary by tube type. However, correlations for some biomarkers support harmonization across types, suggesting cautious optimism for use in banked blood.