The effect of Aβ seeding is dependent on the presence of knock-in genes in the App NL- G- F mice

Sean G Lacoursiere; Jiri Safar; David Westaway; Majid H Mohajerani; Robert J Sutherland

doi:10.3389/frdem.2022.941879

The effect of Aβ seeding is dependent on the presence of knock-in genes in the App ^{NL- G- F} mice

Front Dement. 2022 Sep 12:1:941879. doi: 10.3389/frdem.2022.941879. eCollection 2022.

Authors

Sean G Lacoursiere¹, Jiri Safar², David Westaway³, Majid H Mohajerani¹, Robert J Sutherland¹

Affiliations

¹ Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, Canada.
² Departments of Pathology, Neurology, Psychiatry, and National Prion Disease Pathology Surveillance Center, School of Medicine, Case Western Reserve University, Cleveland, OH, United States.
³ Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB, Canada.

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 a 2-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 3 months of age or 1 month following seeding, spatial learning and memory were tested using the Morris water task. Immunohistochemical labeling showed seeding with the Aβ was found accelerate Aβ plaque deposition and microgliosis in the App ^NL-G-F mice, but this was dependent on the presence of the knocked-in genes. However, we found no correlation between pathology and spatial performance. The results of the present study show the seeding effects in the App ^NL-G-F knock-in model, and how these are dependent on the presence of a humanized App gene. But these pathological changes were not initially causal in memory impairment.

Keywords: Alzheimer's disease; amyloid-β; memory; mice; microglia; seeding.