Animal models of Alzheimer disease

Abstract

Significant insights into the function of genes associated with Alzheimer disease and related dementias have occurred through studying genetically modified animals. Although none of the existing models fully reproduces the complete spectrum of this insidious human disease, critical aspects of Alzheimer pathology and disease processes can be experimentally recapitulated. Genetically modified animal models have helped advance our understanding of the underlying mechanisms of disease and have proven to be invaluable in the preclinical evaluation of potential therapeutic interventions. Continuing refinement and evolution to yield the next generation of animal models will facilitate successes in producing greater translational concordance between preclinical studies and human clinical trials and eventually lead to the introduction of novel therapies into clinical practice.

Figure 1.

Visualization of amyloid plaques in 3xTg-AD mice with classical stains. 3xTg-AD mice develop diffuse and fibrillar plaques, as detected with antibody 6E10 (A and B), thioflavin-S (C), Congo red (D), and Gallyas stain (E).

Figure 2.

3xTg-AD mice develop Gallyas-positive intraneuronal tangles. Age-dependent accumulation of Gallyas-positive aggregates within hippocampal neurons are observed in 3xTg-AD mice.

Figure 3.

Pathways by which Aβ facilitates tau pathology. Several pathways have been implicated in the hyperphosphorylation and aggregation of tau in neurons. These include inflammation, proteasome impairments, impairments in autophagy, increased kinase activity, and decreased phosphatase activity, as well as impeded axonal transport.