Alzheimer’s disease

alzheimers-diseaseMouse models of Alzheimer’s disease (AD) are widely used to study amyloid-beta (Aβ) oligomerization, amyloid plaque formation and their consequences, such as Aβ-induced pathology and cognitive decline.

Alzheimer’s disease pathology

AD is a progressive, highly debilitating disease that is associated with cognitive decline. An early event in the pathology of AD is the oligomerization of Aβ and the formation of amyloid plaques. These protein aggregates, whose formation is due to an imbalance between the production of Aβ from APP, and clearance of Aβ, are thought to underlie downstream pathology, including synaptic toxicity, neurodegeneration and inflammation.

Mouse models and behavioural readouts of AD

Mouse models of AD carry human mutations that cause early-onset familial AD. These mutations lead to increased production of Aβ and a shift towards the production of Aβ42, the most toxic Aβ species. These mouse models develop amyloid plaques and severe cognitive impairments by 6 months of age (i.e. Morris Water Maze, T-maze). However, recent studies by us and others show that cognitive impairments can already be detected before plaque onset (i.e. CognitionWall™ Discrimination learning, Fear conditioning, Nesting test)1.

Therapeutic strategies

Various treatment options can be tested in AD mouse models. For instance, acute treatment with a BACE1 inhibitor, an enzyme critically involved in the generation of toxic Aβ species, effectively reduces the amount of Aβ42 in brain tissue a few hours after treatment. In addition to the analysis of Aβ levels in the brain, cerebrospinal fluid, and blood using ELISA, the number and size of amyloid plaques can be quantified after immunohistochemical staining of brain slices of mouse models of AD.

1Reducing hippocampal extracellular matrix reverses early memory deficits in a mouse model of Alzheimer’s disease. Végh et al., Acta Neuropathol Commun. 2014; 2:76