糖心原创

Alzheimer鈥檚 disease (AD), a complex, multifactorial neurodegenerative disease, is challenging to study in vitro due to a lack of physiologically relevant models. ioGlutamatergic Neurons carrying the PSEN1 M146L and APP V717I mutations secreted significantly more A尾42 compared to their wild type control, showing higher A尾42:40 ratios. A clear correlation between genotype and A尾42:40 ratios was observed, as wild type, heterozygous and homozygous mutants showed a stepwise increase in A尾42 production relative to A尾40. ioGlutamatergic Neurons APP KM670/671NL secreted significantly more A尾38, A尾40, and A尾42 than their wild type control, but the A尾42:40 ratio did not increase, as expected.

ioGlutamatergic Neurons with mutations in PSEN1 or APP recapitulate the increase in A尾42 secretion observed in Alzheimer鈥檚 patients, demonstrating their validity as an in vitro model to study AD and for the discovery of drugs targeting the pathogenic A尾 pathway.