Development of the synaptic dysfunction index and its association with beta-amyloid in preclinical stages of Alzheimer’s disease

Background: Synaptic dysfunction is an early event in Alzheimer’s disease and may be related to amyloid-beta deposits in preclinical stages. Objective: To develop the Synaptic Dysfunction Index (IDsyn) and evaluate its association with amyloid-beta. Method: Analytical study with secondary data (n = 375). Principal Component Analysis (PCA) was applied to derive the IDsyn from neurogranin, SNAP25, SYT1, and GAP43. Associations with amyloid-beta were analyzed, and discriminatory capacity was assessed with ROC curves. Results: PCA explained 86.7% of the variability, with neurogranin, SYT1, and GAP43 as the main contributors. The presence of amyloid-beta was associated with higher IDsyn (p < 0.001), especially at high levels (OR: 16.65; 95% CI: 3.80-72.87). The ROC curve showed good discriminatory ability (AUC: 0.794). Conclusion: IDsyn quantifies synaptic dysfunction and is associated with elevated beta-amyloid levels.