Prognostic value of plasma NfL and GFAP for conversion to Alzheimer's disease and dementia in MCI: a systematic review and robust Bayesian meta-analysis

Accessible biomarkers to predict conversion to Alzheimer's disease and other dementias in Mild Cognitive Impairment (MCI) are urgently needed. Plasma neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) are leading candidates, but their utility remains debated.

We systematically reviewed the prognostic value of plasma NfL and GFAP in MCI using Robust Bayesian Meta-Analysis (RoBMA) to formally model and adjust for publication bias.

We searched major databases through September 2025 for longitudinal cohort studies (Protocol: OSF 10.17605/OSF.IO/974ZD). RoBMA synthesized hazard ratios while adjusting for small-study effects. Risk of bias (QUIPS) and certainty (GRADE) were assessed.

We included 63 studies. For plasma GFAP (k = 3), Bayesian meta-analysis found moderate evidence for an association with dementia conversion (HR: 1.58, 95% CrI [1.00, 2.24]; Inclusion BF = 9.03). Conversely, for plasma NfL, the prognostic signal was driven by decisive publication bias (Bias BF > 4,000,000). After bias adjustment, the effect of NfL on conversion was null (HR: 1.00; Inclusion BF = 0.011). Evidence certainty was Low to Very Low.

The prognostic value of plasma NfL for dementia conversion appears to be an artifact of publication bias. Plasma GFAP shows a promising but preliminary signal requiring high-quality validation.