CSF Biomarkers in Longitudinal Alzheimer Disease Cohorts: Pre-Analytic Challenges.

Abstract

BACKGROUND:

The sensitivity of amyloid to pre-analytic factors complicates cerebrospinal fluid (CSF) diagnostics for Alzheimer disease. We report reliability and validity evidence for automated immunoassays from frozen and fresh CSF samples in an ongoing, single-site research program.

METHODS:

CSF samples were obtained from 2 Wisconsin cohorts (1256 measurements; 727 participants). Levels of amyloid beta 1-42 (Aβ42), phosphorylated tau 181 (pTau181), and total tau (tTau) were obtained using an Elecsys cobas e 601 platform. Repeatability and fixed effects of storage tube type, extraction method, and freezing were assessed via mixed models. Concordance with amyloid positron emission tomography (PET) was investigated with 238 participants having a temporally proximal PET scan.

RESULTS:

Repeatability was high with intraclass correlation (ICC) ≥0.9, but tube type strongly affected measurements. Discriminative accuracy for PET amyloid positivity was strong across tube types (area under the curve [AUC]: Aβ42, 0.87; pTau181Aβ42 , 0.96), although optimal thresholds differed.

CONCLUSIONS:

Under real-world conditions, the Elecsys platform had high repeatability. However, strong effects of pre-analytic factors suggest caution in drawing longitudinal inferences.

• Authors: Erin M Jonaitis, Beckie Jeffers, Monica VandenLangenberg, Yue Ma, Carol Van Hulle, Rebecca Langhough, Lianlian Du, Nathaniel A Chin, Robert J Przybelski, Kirk J Hogan, Bradley T Christian, Tobey J Betthauser, Ozioma C Okonkwo, Barbara B Bendlin, Sanjay Asthana, Cynthia M Carlsson, Sterling C Johnson
• Journal: Clinical chemistry (Clin Chem) Vol. 70 Issue 3 Pg. 538-550 (03 02 2024) ISSN: 1530-8561 [Electronic] England
• PMID: 38431278 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © Association for Diagnostics & Laboratory Medicine 2024.

Chemical References

• Amyloid beta-Peptides
• tau Proteins
• Biomarkers
• Peptide Fragments

Topics

• Humans
• Alzheimer Disease (diagnosis, cerebrospinal fluid)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Reproducibility of Results
• tau Proteins (cerebrospinal fluid)
• Positron-Emission Tomography
• Biomarkers (cerebrospinal fluid)
• Peptide Fragments (cerebrospinal fluid)