Abstract Alzheimer’s disease (AD) is characterized by the prion-like propagation of amyloid-β (Aβ). However, the role of Aβ in cognitive impairment is still unclear. To determine the causal role of Aβ in AD, we intracerebrally seeded the entorhinal cortex of two-month-old App NL-G-F mouse model with an Aβ peptide derived from patients who died from rapidly progressing AD. When the mice were three and six months of age, or one- and four-months following seeding, respectively, spatial learning and memory were tested using the Morris water task. Immunohistochemical labeling showed seeding with the Aβ seed increased plaque size one month following seeding, but reduced plaque counts four months following injection compared to the control seeded mice. A significant increase in microgliosis was found. However, we found no correlation between pathology and spatial performance. The results of the present study show that seeding human tissue with or without Aβ alters learning and memory ability, Aβ plaque deposition, plaque size, and microgliosis in the App NL-G-F knock-in model, and these effects are dependent on the presence of a humanized App gene and the presence of Aβ in the seed. But these pathological changes were not initially causal in memory impairment.

Amyloid-β seeding effects are dependent on the presence of knock-in genes in the AppNL-G-F mice