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iPS-derived and trans-differentiated human neurons as models to study Alzheimer’s disease

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Recent groundbreaking work in stem cell biology has made it possible to reprogram non-neuronal cells obtained from Alzheimer’s diseased patients into neurons. For the first time, the research community has the means to study diseased human neurons from Alzheimer’s patients. These models have already yielded novel insights into the disease. However, different reprogramming techniques and various sources of cell material have been used to generate these models, and it is currently unclear whether one approach provides an advantage over the other (in terms of phenotype robustness and disease-relevance). Here, we propose to derive PSEN1-mutant neurons in two distinct ways, i.e., from induced pluripotent stem cells (iPSCs) or directly from fibroblasts by trans-differentiation. We will then characterize the epigenetic signatures of these neurons and determine if the two reprogramming techniques yield phenotypically similar neurons or if one set more closely resembles adult, aged neurons from diseased patients.