The Tg2576 mouse model in biomedical research on Alzheimer's disease

Nowadays Alzheimer’s disease (AD) affects about 5% of people over 60 years old all over the world and in Italy are estimated about 500 thousand patients. AD is a neurodegenerative disease; its pathogenesis is caused by extracellular aggregates of amyloid β (Aβ) plaques and intracellular neurofibrillary tangles made of hyperphosphorylated τ-protein (Tau), a microtubule‐associated protein that under physiological conditions, regulates the assembly and maintenance of the structural stability of microtubules. When neurons in cortical and limbic areas of the human brain are affected by this alteration clinically there is a progressive memory loss and neurocognitive dysfunction. To study pathogenesis of AD many transgenic mouse breeds have been created, and one of the most widely used is the Tg2576 mouse. This model carries the transgene coding for the human 695 splice-variant of amyloid-β precursor protein (APP) for Alzheimer’s amyloid-β (Aβ), which contains the double mutation K670M, N671L (Swedish mutation) driven by a hamster prion protein gene promoter (APP695SWE). This transgenic mouse, expressing high concentrations of the mutant Aβ, develops significant amyloid plaques and shows memory deficits. This represents a particularly useful tool for the study of APP expression, amyloid plaque formation, neuronal decline and memory loss associated with AD, as well as the study of drugs designed for the treatment or prevention of Alzheimer's disease.