Interactions between beta-amyloid and synaptic proteins in neurogranin modulation in the preclinical phase of Alzheimer's disease

Introduction Neurogranin is key in synaptic signaling. Understanding its interaction with beta-amyloid protein is crucial. Proteins such as SYT1, GAP43, and SNAP25 could mediate this effect. Objective To determine whether neurogranin is modulated by beta-amyloid protein through its interaction with synaptic biomarkers in preclinical stages of Alzheimer's disease. Materials and methods This is a secondary data analysis study consisting of 339 adults with and without the presence of beta-amyloid in cerebrospinal fluid (CSF) and/or positron emission tomography. CSF concentrations of neurogranin, SYT1, GAP43, and SNAP25 were analyzed. A parallel mediation model (Hayes PROCESS 4 model) was used to estimate the direct and indirect effects of amyloid-beta on neurogranin, mediated by synaptic biomarkers. The significance of indirect effects was assessed using bootstrapping with 5,000 resamples, generating 95% confidence intervals. Results Multiple linear regression models showed significant associations between amyloid-beta and SYT1, GAP43, and SNAP25. The coefficients were 34.104 (SYT1), 3.652464 (GAP43), and 12.371 (SNAP25); however, there was no significant direct effect between amyloid-beta and neurogranin (p = 0.688). The indirect effects through SYT1 and GAP43 showed significant influences on neurogranin (effects of 269,921 and 658,495, respectively). The indirect effect mediated by SNAP25 was not significant. Conclusions Although beta-amyloid protein was not directly associated with neurogranin, its influence is exerted indirectly through synaptic mediators such as SYT1 and GAP43. These findings reinforce the importance of synaptic pathways in preclinical stages of Alzheimer's disease.