Abstract
Human models of Alzheimer's disease (AD) have the potential to complement existing animal models for carrying out functional studies of AD pathogenesis and the development of novel therapies. An effective human cellular model of AD would use the appropriate cell types and ideally neural circuits affected by the disease, would develop relevant pathology and would do so in a reproducible manner over a timescale short enough for practical use. A pressing question for the usefulness of this approach is whether neurological diseases that take decades to become manifest in humans can be successfully modelled over a reasonable timescale. We discuss here whether these models can do more than simply replicate what is already known about AD, and evaluate some of their potentially unique advantages.
Highlights
Human models of Alzheimer’s disease (AD) have the potential to complement existing animal models for carrying out functional studies of AD pathogenesis and the development of novel therapies
A number of questions remain over the utility of this approach, including the degree to which stem cell models will be of use in diseases such as AD in which several different neuronal types in discrete regions of the nervous system are affected by the disease process [14]
Cellular models of AD and AD-related disorders have been reported in the past year by several research groups [8,9,10,13]. Those studies clearly demonstrated that neurons generated from genetic forms of AD both from induced pluripotent stem cell (iPSC) and by direct transdifferentiation recapitulate key aspects of AD pathology, altered amyloid precursor protein (APP) processing and Abeta fragment of APP protein (Aβ) peptide production
Summary
Human models of Alzheimer’s disease (AD) have the potential to complement existing animal models for carrying out functional studies of AD pathogenesis and the development of novel therapies. Approaches to generating human neurons and neural circuits The combination of novel, powerful stem cell technologies, most notably cellular reprogramming [2,3,4], with the maturation of the field of developmental biology has enabled considerable progress in our ability to generate specific neuronal cell types in vitro.
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