Induced Pluripotent Stem Cell-Derived Neural Culture Model of Alzheimer’s Disease: A 3D Organoid Approach

Abstract

Alzheimer’s disease (AD) is a progressive neurologic disorder that impacts a diverse population of older adults. As three-dimensional (3D) models are powerful tools for advancing AD studies, the authors have been developed AD cortical organoids to enable the observation of AD pathology at the cellular, tissue, and organ levels. For creating the model, APPSwe/Ind (APP) and PSEN1 (PS1) mutant genes were transfected into mouse induced pluripotent stem cells (iPSCs) following which the iPSC lines that expressed mutant APP and PS1 proteins were obtained. Then, using modified serum-free suspended embryoid body culture, AD cerebral organoids were made successfully at various ages. The AD model can show AD’s biochemical and pathological alterations, such as overexpressions of Aβ40 and Aβ42 and a decrease of GABAergic interneurons. The proposed model has the potential for implementation in many biomedical applications, including AD drug screening, stem cell transplant, and neuronal tissue engineering.