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 [ $A\beta ]{}_{42}$ , $A{\beta }_{40}$ , $\mathrm{phosphorylated}\mathrm{tau}[p-\mathrm{ta}{u}_{181}$ , total tau [t-tau], neurofilament light chain [NfL], $A{\beta }_{\frac{42}{40}},$ and $\frac{p-\mathrm{ta}{u}_{181}}{A{\beta }_{42}}$ ) 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 ( $R^2$ = 0.94), adequate for amyloid ( $R^2$ = 0.40-0.69), and weaker for t-tau ( $R^2$ = 0.04-0.42) and $p-\mathrm{ta}{u}_{181}$ ( $R^2$ = 0.22-0.29). Brain amyloidosis differentiated several measures, especially EDTA plasma $\frac{\mathrm{pTa}{u}_{181}}{A{\beta }_{42}}$ ( $d$ = 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.