Transgenic mouse models of Alzheimer disease: developing a better model as a tool for therapeutic interventions

Abstract

Alzheimer disease (AD) is the leading cause of dementia among elderly. Currently, no effective treatment is available for AD. Analysis of transgenic mouse models of AD has facilitated our understanding of disease mechanisms and provided valuable tools for evaluating potential therapeutic strategies. In this review, we will discuss the strengths and weaknesses of current mouse models of AD and the contribution towards understanding the pathological mechanisms and developing effective therapies.

Fig. (1). Schematic diagram of APP mutations and its amyloidogenic effect

Amyloid precursor protein (APP) is a type I transmembrane protein, and within its sequence, amyloid-β(Aβ) resides. APP is proteolytically cleaved by α-, β-, and γ-secretase activities, and α-secretase cleavage precludes toxic Aβ to be produced. FAD-linked genetic mutations on APP exhibit different effects on APP processing and amyloidogenic properties of Aβ peptides. Please refer main text for detailed explanation.