Biomarkers.

Background: We performed a systematic review and meta-analysis of blood astrocyte biomarkers in Alzheimer's disease (AD).

Method: MEDLINE and Web of Science were searched without any restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, and S100B in AD patients. Pooled effect sizes were determined using Hedge's g method with a random effects model. The review was prospectively registered on PROSPERO (registration number CRD42023458305).

Result: The search identified 1186 studies; 36 met inclusion criteria (n=3366 AD patients, n=4115 cognitively unimpaired [CU]). Compared to CU individuals, AD patients had significantly higher GFAP and YKL-40 levels (GFAP effect size 1.15, 95% CI 0.94-1.36, P<.0001; YKL-40 effect size 0.38, 95% CI 0.28-0.49, P<.0001). Both biomarkers showed a trend towards a greater effect size in more advanced disease. No significant difference in blood S100B levels were identified.

Conclusion: Our findings reveal significant elevations in blood GFAP and YKL-40 levels in AD patients across the clinical spectrum, suggesting that both biomarkers accurately reflect AD-related pathology.