An exploration of amyloid-β seeding in mouse models of dementia

Thumbnail Image
Lacoursiere, Sean
University of Lethbridge. Faculty of Arts and Science
Journal Title
Journal ISSN
Volume Title
Lethbridge, Alta. :University of Lethbridge, Dept. of Neuroscience
Alzheimer’s disease (AD) is characterized by the prion-like propagation of misfolded proteins that appears dependent on the initial accumulation of amyloid-β (Aβ). But the role of Aβ in cognitive impairment is still unclear. To determine the causal role of Aβ in AD, mouse models expressing pathological features of AD were intracerebrally seeded with Aβ. Behavioural and immunohistochemical techniques were used to assess the effects of seeding. Seeding was found to increase Aβ plaque deposition and microgliosis throughout the brain after a brief inoculation period. The effect was dependent on the presence of specific knocked-in genes. Seeding was also found to increase the presence of tau hyperphosphorylation in isolated parts of the brain. Yet, no significant correlation between pathology and memory was found. In summary, large increases in Aβ plaque and microgliosis do not initially cause cognitive impairment. Suggesting other underlying disease processes may be driving cognitive decline in AD.
Neuroscience , Alzheimer's , Seeding , Molecular , Behavioural