PROGRESSIVE PODOPLANIN UPREGULATION AND AMYLOID PLAQUE-ASSOCIATED LOCALIZATION IN THE 5×FAD ALZHEIMER’S DISEASE MOUSE MODEL

Alzheimer’s disease (AD) is characterized by progressive cognitive decline and pathological hallmarks including amyloid β (Aβ) plaque accumulation and neuroinflammation. Podoplanin is a small mucin-like glycoprotein involved in several physiological and pathological processes in the brain including development, angiogenesis, tumors, ischemic stroke and other neurological disorders. However, its temporal regulation and pathological association in AD remain incompletely understood. In this study, we examined age-dependent changes in PDPN expression and its spatial association with Aβ pathology in the 5×FAD (five familial Alzheimer’s disease) mouse model at 3, 6, and 12 months of age. Hippocampal tissues from 5×FAD and wild-type (WT) mice were analyzed by Western blotting to quantify PDPN protein levels. Regional distribution patterns were examined using whole-brain immunohistochemistry (IHC), and plaque-associated localization was further assessed by double immunofluorescence staining for Aβ and PDPN. The 5×FAD mice exhibited a progressive, age-dependent increase in hippocampal PDPN expression compared with WT controls across all time points. Consistently, whole-brain IHC revealed robust PDPN immunoreactivity broadly distributed throughout the brain, with particularly strong expression in AD-vulnerable regions including the cortex and hippocampus. Furthermore, double immunofluorescence demonstrated plaque-associated accumulation of PDPN signals. PDPN signals also showed apparent spatial colocalization with Aβ deposits, suggesting that PDPN upregulation is associated with amyloid pathology progression. Taken together, these findings indicate a potential relationship between Aβ deposition and PDPN upregulation during AD progression in 5×FAD mice.