Diagnostic and prognostic role of serum/plasma and CSF amyloid beta peptide levels in traumatic brain injury: a systematic review and meta-analysis.

Amyloid beta (Aβ) peptides, particularly Aβ1-40 and Aβ1-42, have been implicated in TBI pathology as potential biomarkers for diagnosis and prognosis. This systematic review and meta-analysis aimed to evaluate differences in Aβ levels between TBI and non-TBI populations and their prognostic utility in both acute and chronic phases of TBI. A systematic search of MEDLINE, Scopus, and Web of Science was conducted up to October, 2024, with an updated search in July 2025. Studies assessing Aβ1-40 or Aβ1-42 in cerebrospinal fluid (CSF) or plasma of adults with TBI were included. Risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed for between-group comparisons, with subgroup analyses based on biological compartment and sampling interval. 25 studies were included in the review and 11 underwent quantitative synthesis. Qualitative evaluation of studies suggested a positive correlation between Aβ1-42 and neurological status in moderate to severe TBI but not mild TBI or concussion. Plasma Aβ1-42 levels were significantly elevated in TBI patients within 24 h post-injury (SMD:0.91, 95%CI: [0.15-1.66 No significant differences were observed in CSF (SMD:-0.37, 95%CI: [-0.88-0.15]) or plasma Aβ1-42 (SMD:0.09, 95%CI: [-0.07-0.26]) or Aβ1-40 (SMD:0.10 95%CI: [-0.25-0.44]) levels beyond the first year following TBI. Aβ peptides, particularly Aβ1-42, appear to change acutely in plasma post-TBI but show no consistent long-term alterations in either plasma or CSF. The limited and heterogeneous evidence suggests only modest prognostic potential, with no current support for their clinical use as reliable biomarkers for diagnosis or prognosis in TBI. Further large-scale, standardized studies are warranted.