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

Erin M Jonaitis; Henrik Zetterberg; Rebecca Langhough Koscik; Tobey J Betthauser; Carol A Van Hulle; Kirk Hogan; Laura Hegge; Gwendlyn Kollmorgen; Ivonne Suridjan; Carey E Gleason; Corinne D Engelman; Ozioma C Okonkwo; Sanjay Asthana; Barbara B Bendlin; Cynthia M Carlsson; Sterling C Johnson; Kaj Blennow

doi:10.1002/dad2.12266

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

Alzheimers Dement (Amst). 2022 Feb 9;14(1):e12266. doi: 10.1002/dad2.12266. eCollection 2022.

Authors

Erin M Jonaitis^{1

2}, Henrik Zetterberg^{3

4

5

6

7}, Rebecca Langhough Koscik^{1

2}, Tobey J Betthauser², Carol A Van Hulle², Kirk Hogan⁸, Laura Hegge¹, Gwendlyn Kollmorgen⁹, Ivonne Suridjan¹⁰, Carey E Gleason^{11

2}, Corinne D Engelman^{2

12}, Ozioma C Okonkwo², Sanjay Asthana^{11

2}, Barbara B Bendlin², Cynthia M Carlsson^{11

1

2}, Sterling C Johnson^{11

1

2}, Kaj Blennow^{3

4}

Affiliations

¹ School of Medicine and Public Health Wisconsin Alzheimer's Institute University of Wisconsin-Madison Madison Wisconsin USA.
² Wisconsin Alzheimer's Disease Research Center School of Medicine and Public Health University of Wisconsin-Madison Madison Wisconsin USA.
³ Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology University of Gothenburg Mölndal Sweden.
⁴ Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology Sahlgrenska University Hospital Mölndal Sweden.
⁵ Department of Neurodegenerative Disease UCL Institute of Neurology London UK.
⁶ UK Dementia Research Institute at UCL London UK.
⁷ Hong Kong Center for Neurodegenerative Diseases Hong Kong China.
⁸ Department of Anesthesiology School of Medicine and Public Health University of Wisconsin-Madison Madison Wisconsin USA.
⁹ Roche Diagnostics GmbH Penzberg Germany.
¹⁰ Roche Diagnostics International Ltd Rotkreuz Switzerland.
¹¹ Geriatric Research Education and Clinical Center of the Wm. S. Middleton Memorial Veterans Hospital Madison Wisconsin USA.
¹² Department of Population Health Sciences University of Wisconsin-Madison Madison Wisconsin USA.

Abstract

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 [ $A β]_{42}$ , $A β_{40}$ , $phosphorylated tau [p - ta u_{181}$ , total tau [t-tau], neurofilament light chain [NfL], $A β_{\frac{42}{40}},$ and $\frac{p - ta u_{181}}{A β_{42}}$ ) 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 $p - ta u_{181}$ ( $R^{2}$ = 0.22-0.29). Brain amyloidosis differentiated several measures, especially EDTA plasma $\frac{pTa u_{181}}{A β_{42}}$ ( $d$ = 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.

Keywords: Alzheimer's disease; amyloid beta; cognitively unimpaired; neurofilament light; plasma; p‐tau181; t‐tau.

Abstract

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