Aβ plaque deposition and microgliosis following Aβ seeding in AppNL-G-F mice is regionally distinct

Abstract Background. Alzheimer’s disease (AD) is characterized by the prion-like propagation of amyloid-β (Aβ). However, the role of Ab in cognitive impairment is still unclear. Methods. Two-month-old AppNL-G-F were intracerebrally seeded with three conformationally distinct Aβ seeds. The mice were trained in a multi-model paradigm using multiple behavioural tests. Immunohistochemical techniques were used to assess Ab deposition, microgliosis, and cholinergic tone. Results. Seeding accelerated AD pathology throughout the brain in a region-dependent manner. Microgliosis was elevated in the substantia nigra reticular area. The cholinergic tone was found to be significantly reduced in the medial septal band. No impairment in learning and memory was found. Conclusion. These results suggest seeding accelerates microglial and Ab plaque progression in a regional distinct manner with the seed having no unique effect on behaviour or histological markers.