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.
Accurate prognosis in Mild Cognitive Impairment (MCI) is essential for patient counseling and clinical trial enrichment. While plasma NfL and GFAP are widely promoted as accessible biomarkers, their predictive reliability across heterogeneous populations remained uncorrected for publication bias. Our findings demonstrate that the prognostic value of plasma NfL is largely a statistical artifact; its use as a standalone predictor for dementia conversion lacks clinical utility in mixed MCI cohorts. Conversely, plasma GFAP shows a promising, though preliminary, signal. Clinicians should exercise caution when using these biomarkers for individual risk assessment until more specific, bias-adjusted validation is available.

目前迫切需要可用于预测轻度认知障碍（Mild Cognitive Impairment, MCI）患者进展为阿尔茨海默病及其他痴呆的可及性生物标志物。血浆神经丝轻链蛋白（neurofilament light, NfL）与胶质纤维酸性蛋白（glial fibrillary acidic protein, GFAP）是极具潜力的候选标志物，但其临床应用价值仍存在广泛争议。
本研究采用稳健贝叶斯Meta分析（Robust Bayesian Meta-Analysis, RoBMA）对轻度认知障碍患者血浆NfL与GFAP的预后价值开展系统综述，以正式建模并校正发表偏倚。
我们于2025年9月前在主要学术数据库中检索了纵向队列研究，研究方案为OSF 10.17605/OSF.IO/974ZD。RoBMA在校正小样本效应的前提下合并风险比（hazard ratio, HR）数据，并采用QUIPS工具评估偏倚风险、GRADE工具评估证据确定性。
本研究共纳入63项相关研究。针对血浆GFAP（k=3），贝叶斯Meta分析结果显示，其与痴呆进展存在关联的证据等级为中等（HR=1.58，95%可信区间CrI[1.00, 2.24]；纳入贝叶斯因子Inclusion BF=9.03）。与之相反，血浆NfL的预后信号实则由显著的发表偏倚主导（偏倚贝叶斯因子Bias BF>4,000,000）。经偏倚校正后，NfL对痴呆进展的影响效应归零（HR=1.00；Inclusion BF=0.011），证据确定性为低至极低。
血浆NfL用于痴呆进展的预后价值似乎是发表偏倚导致的统计假象。血浆GFAP则展现出具有潜力但仍需进一步验证的初步信号。
对轻度认知障碍患者进行精准预后评估，对于患者咨询与临床试验富集均至关重要。尽管血浆NfL与GFAP作为可及性生物标志物被广泛推广，但其在异质性人群中的预测可靠性尚未经发表偏倚校正。本研究结果表明，血浆NfL的预后价值在很大程度上属于统计假象；在混合MCI队列中，将其作为痴呆进展的独立预测因子缺乏临床应用价值。与之相反，血浆GFAP虽仍处于初步研究阶段，但展现出了具有潜力的信号。临床医生在使用上述生物标志物开展个体风险评估时应谨慎行事，直至获得更具特异性、经偏倚校正的验证数据。