Parallelism in Neurodegenerative Biomarker Tests: Hidden Errors and the Risk of Misconduct

TL;DR

This systematic review highlights that partial parallelism in neurodegenerative biomarker assays is rarely reported and inconsistently documented, risking biased results and emphasizing the need for standardized validation and transparent reporting.

Contribution

The paper provides a comprehensive analysis of parallelism issues in neurodegenerative biomarker tests, revealing gaps in reporting and suggesting improvements for assay validation.

Findings

Partial parallelism is infrequently observed in studies.

Reporting of parallelism is inconsistent and often incomplete.

Methodological limitations hinder generalizability of results.

Abstract

Biomarkers are critical tools in the diagnosis and monitoring of neurodegenerative diseases. Reliable quantification depends on assay validity, especially the demonstration of parallelism between diluted biological samples and the assay's standard curve. Inadequate parallelism can lead to biased concentration estimates, jeopardizing both clinical and research applications. Here we systematically review the evidence of analytical parallelism in body fluid (serum, plasma, cerebrospinal fluid) biomarker assays for neurodegeneration and evaluate the extent, reproducibility, and reporting quality of partial parallelism. This systematic review was registered on PROSPERO (CRD42024568766) and conducted in accordance with PRISMA guidelines. We included studies published between December 2010 to July 2024 without language restrictions. ... In conclusion, partial parallelism was infrequently observed and inconsistently reported in most biomarker assays for neurodegeneration. Narrow dilution ranges and variable methodologies limit generalizability. Transparent reporting of dilution protocols and adherence to established analytical validation guidelines is needed. This systematic review has practical implications for clinical trial design, regulatory approval processes, and the reliability of biomarker-based diagnostics.