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

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).

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 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).

AD biomarker concentrations vary by tube type. However, correlations for some biomarkers support harmonization across types, suggesting cautious optimism for use in banked blood.