Exploratory effects of coffee-derived exosome-like nanoparticles in a fibrillar amyloid-beta 1–42-induced neurodegenerative rat model: evidence from fluorodeoxyglucose positron emission tomography and phosphorylated tau/amyloid precursor protein expr

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta 1–42 (Aβ 1–42 ) accumulation, tau pathology, and metabolic dysfunction. This exploratory study evaluated the effects of coffee-derived exosome-like nanoparticles (CELNs) on selected metabolic and histopathological endpoints in a fibrillar Aβ 1–42 -induced neurodegenerative rat model. Methods Fifty male Sprague–Dawley rats were randomly divided into five groups ( N = 10 each): Control (C), sham (SF), a fibrillar Aβ 1–42 -induced neurodegenerative rat model (AD), AD treated with a low dose of CELNs (AD + LE, 10 mg/kg/day), and AD treated with a high dose of CELNs (AD + HE, 20 mg/kg/day) for 14 days. CELNs were quantified and characterized using the bicinchoninic acid method, scanning electron microscopy, and nanoparticle tracking analysis (NTA). Micro-positron emission tomography/computed tomography fluorodeoxyglucose (MicroPET/CT FDG) imaging of the central nervous system was performed in all groups at the end of treatment. Subsequently, all animals were sacrificed, and hippocampal tissues were subjected to histopathological analysis. Results MicroPET imaging demonstrated a significant, dose-dependent increase in cerebral glucose metabolism in AD rats treated with CELNs compared with the untreated AD group. Histopathological evaluations were consistent with the imaging data: in AD groups receiving CELNs, phospho-tau and beta-amyloid precursor protein expression were significantly reduced in the hippocampal cornu ammonis 2 (CA2) and dentate gyrus regions compared with the untreated AD group. Conclusions In this exploratory fibrillar Aβ 1–42 -induced neurodegenerative rat model, oral CELN administration was associated with dose-dependent partial improvements in cerebral glucose metabolism and region-specific reductions in hippocampal phosphorylated tau (p-Tau) and amyloid precursor protein (APP) immunoreactivity. However, these are preliminary biomarker-level findings that support further investigation of CELNs; definitive confirmation of functional and cognitive benefits requires additional behavioral, biodistribution, and experimental validation.