Objective: Investigate the diagnostic value of cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) in AD and the predictive value of AD transition from mild cognitive impairment (MCI) to dementia through a cross-sectional and longitudinal observational study. Methods: 787 subjects with CSF GAP-43 data were divided into normal group (n=247), MCI group (n=413) and dementia group (n=127) based on cognitive status. Kruskal-Wallis test was used to compare the differences of CSF GAP-43 between groups. Multiple logistic model was used to test the correlation between CSF GAP-43 and different cognitive states. The diagnostic efficacy of CSF GAP-43 level for AD was evaluated by receiver-operating curves (ROC) and the area under curves (AUC). The diagnostic efficacy of AD was compared with that of CSF core markers (Aβ, t-tau, p-tau). Patients with MCI were divided into stable MCI (sMCI) and progressive MCI (pMCI) according to whether they progressed to dementia within 5 years. Mann-Whitney u test was used to compare CSF GAP-43 between groups. Cox regression model was used to test the correlation between CSF GAP-43 and the progression of MCI to dementia. The predictive value of CSF GAP-43 levels in predicting MCI progression to dementia was evaluated by ROC curve. The association of CSF GAP-43 level with the risk of progression to dementia was evaluated using Kaplan-Meier survival curves. Results: The results of cross-sectional study showed that the level of CSF GAP-43 was significantly higher in the dementia group than in the normal group and the MCI group (P<0.0001). CSF GAP-43 was an independent risk factor for the onset of AD dementia (P=0.002). The AUC of CSF GAP-43, Aβ, p-tau and t-tau for the diagnosis of AD were 0.64, 0.68, 0.64 and 0.63. Follow-up analysis showed that the level of CSF GAP-43 in pMCI patients was significantly higher than that in sMCI patients (P<0.0001), and CSF GAP-43 was an independent risk factor for the progression of MCI to dementia (P=0.012). The AUC for CSF GAP-43 predicting MCI progression to dementia was 0.75 (P<0.0001, 95%CI: 0.69~0.80). The risk of progression to dementia was 3.45 times greater in MCI patients with high CSF GAP-43 levels than in MCI patients with low CSF GAP-43 levels (P<0.0001, 95%CI: 2.17~5.43).Conclusion: CSF GAP-43 level can be used in the diagnosis of AD dementia, and its diagnostic efficacy is comparable to that of CSF core biomarkers (Aβ, t-tau, p-tau). CSF GAP-43 can predict the progression of MCI to dementia and is an independent risk factor for the progression of MCI to dementia.