Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Generation of an Alzheimer’s Disease Model Derived from Induced Pluripotent Stem Cells with an APP Gene Mutation

Version 1 : Received: 5 May 2024 / Approved: 6 May 2024 / Online: 6 May 2024 (07:37:30 CEST)

How to cite: Kim, Y.; Yun, B.; Ye, B. S.; Kim, B.-Y. Generation of an Alzheimer’s Disease Model Derived from Induced Pluripotent Stem Cells with an APP Gene Mutation. Preprints 2024, 2024050243. https://doi.org/10.20944/preprints202405.0243.v1 Kim, Y.; Yun, B.; Ye, B. S.; Kim, B.-Y. Generation of an Alzheimer’s Disease Model Derived from Induced Pluripotent Stem Cells with an APP Gene Mutation. Preprints 2024, 2024050243. https://doi.org/10.20944/preprints202405.0243.v1

Abstract

Alzheimer’s disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the amyloid precursor protein (APP) gene. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.

Keywords

Alzheimer’s disease; amyloid precursor protein; cerebral organoid; disease modeling; drug screening; induced pluripotent stem cells; organoids; tau pathology

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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