Diagnostic Role of Tau Proteins in Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-Analysis

Abstract

Background. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that currently lacks reliable diagnostic biomarkers. The meta-analysis is performed with an aim to evaluate the diagnostic potential of cerebrospinal fluid (CSF) total tau (t-tau), phosphorylated-tau (p-tau), and their ratio in ALS patients. Methods. A comprehensive search for literature published between the 1st of January 2000 and the 15th of May 2022 was performed in databases PubMed, medRxiv, and Google Scholar. The retrieved articles were first screened by title and abstract, and later, full-text screening was performed based on the eligibility criteria. Data on p-tau and t-tau levels and p-tau/t-tau ratio in ALS patients and controls were extracted, and a meta-analysis was performed using random-effects models in Review Manager version 5.4. Results. Data were analyzed from seven studies reporting p-tau and t-tau levels and their ratio among ALS patients and controls. The number of total study participants was 1,100. In ALS patients, the levels of p-tau didn’t differ significantly with controls (standardized mean difference (SMD): 0.14 (95% CI: -0.41 to 0.70); $p=0.61$ ). In contrast, there were significantly elevated levels of t-tau and significantly lowered p-tau/t-tau ratio in ALS (SMD: 1.76 (95% CI: 0.53 to 2.98); $p=0.005$ and SMD: -3.09 (95% CI: -5.33 to -0.86); $p=0.007$ , respectively). Conclusion. Our meta-analysis study supports the role of core CSF biomarkers of neurodegeneration: t-tau and p-tau/t-tau ratio as a diagnostic biomarker of amyotrophic lateral sclerosis. This study found that t-tau is elevated while p-tau/t-tau ratio is lowered in ALS.