Yagi et al. were the first to generate iPSCs from AD patients, harboring mutations in PSEN1 (A246E) and PSEN2 (N141I) and demonstrated increased Aβ42 secretion along with an elevated Aβ42 to Aβ40 ratio in the iPSC derived neurons as compared to those from non-AD controls. They also studied the response of the secreted Aβ42 levels to a known γ-secretase inhibitor with positive results indicating the potential of candidate drugs for AD treatment.
Another study by Kondo et al. showed intracellular accumulation of Aβ oligomers in both FAD (APP-E693D mutation) and SAD cases, inducing both endoplasmic reticulum (ER) and oxidative stress in the iPSC derived neurons. The accumulated Aβ oligomers were not proteolytically resistant and treatment of the AD neural cells with docosahexaenoic acid (DHA) resulted in alleviation of stress responses, paving the way for the development of anti-AD drugs. Learn more: cell culture models of alzheimer's disease
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