Transgenic animal model for Alzheimer’s disease

Abstract

This patent describes a new transgenic animal model of Alzheimer’s disease (AD). The transgene consists of the human amyloid precursor protein (APP) gene containing one or more of the mutations known to co-segregate with autosomal dominant familial AD (Swedish mutation K670N/M671L; London mutation V717I) linked to a rodent Thy-1 promoter. Qualitative (neuropathological) and quantitative (behavioural, cognitive) outcome measures are reported for transgenic animals aged 6 - 15 months. Neuropathological changes include neuronal and synaptic loss, and senile plaques with associated dystrophic neurites. Furthermore, immunostaining for the microtubule-associated protein tau, which accumulates in a hyperphosphorylated form in the neurofibrillary pathology of AD, is reported to be positive in the dystrophic neurites, the first time that this has been found in an APP transgenic animal model. Hence, it is claimed that this transgenic animal may replicate more faithfully and accurately the neuropathological and clinical phenotype of AD and, thus, supersede previous animal models.

• Alzheimer’s disease
• amyloid
• animal model
• neurofibrillary pathology
• transgenic