Alberto Guevara-Tirado, Facultad de Medicina Humana, Universidad Científica del Sur, Lima, Perú
Background: Amyloid status disrupts synapses by affecting key proteins such as SYT-1, GAP-43, neurogranin, and SNAP-25, thereby interfering with neurotransmission. Objective: To evaluate the effects of amyloid status on SYT-1 through a serial mediation model, considering GAP-43, neurogranin, and SNAP-25 as mediators. Method: An analytical, cross-sectional study was conducted using secondary data from the Dryad repository (n = 339). The PROCESS model 6 for SPSS was applied, with amyloid status as the independent variable, SYT-1 as the dependent variable, and the aforementioned mediators in sequence. Bootstrapping with 5,000 resamples was used, and a directed acyclic graph (DAG) was developed to visualize the causal pathways. Results: Amyloid status was significantly associated with GAP-43 (B = 365.25; p = 0.005), which in turn was related to neurogranin, SNAP-25, and SYT-1. The most relevant indirect pathways were: amyloid status → GAP-43 → SYT-1 (effect: 1.539; 95% CI: 0.489-2.775) and amyloid status → GAP-43 → neurogranin → SYT-1 (effect: 1.601; 95% CI: 0.472-2.928). Conclusion: Amyloid status influences SYT-1 through indirect pathways mediated by synaptic proteins, with GAP-43 emerging as a key mediator.
Keywords: Amyloid beta-peptides. Biomarkers. Synaptotagmin I. Synaptic transmission. Mediation analysis.