Methylation alterations of Fbln1 gene in the hippocampus of PSEN1/PSEN2 double knockout and APP/PS1 transgenic mice

• Fbln1 gene is hypomethylated in the hippocampus of mid-stage AD dKO mice, correlating with increased Fbln1 expression. • Fbln1 mRNA and protein levels are elevated in both dKO (non-Aβ) and DTG (Aβ-depositing) AD mouse models, suggesting a common role in AD pathogenesis. • The lack of significant difference between Fbln1 and Aβ levels in dKO mice indicates Fbln1 may act independently of Aβ deposition. • Fbln1 methylation changes may represent a novel non-Aβ-related mechanism and potential therapeutic target for Alzheimer's disease.