Alzheimer's Disease (AD)
Alzheimer's disease is the leading cause of dementia worldwide, characterized by two defining neuropathological hallmarks: extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. These lesions drive progressive synaptic dysfunction, neuronal loss, and irreversible cognitive decline.
APOE & Genetic Risk
Apolipoprotein E (APOE) is the principal lipid transport protein in the central nervous system and the strongest known genetic risk factor for late-onset AD. Its three major isoforms confer distinct disease susceptibility profiles: APOE ε2 is neuroprotective, APOE ε3 is considered risk-neutral, and APOE ε4 markedly elevates disease susceptibility while accelerating both amyloid deposition and tau pathology.
Brain Organoids as a Disease Model
Human iPSC-derived brain organoids are self-organizing three-dimensional neural tissues that faithfully recapitulate key features of human cortical cytoarchitecture and development. Unlike conventional 2D cultures or rodent models, organoids permit direct interrogation of human-specific neurodegenerative mechanisms in vitro and can provide an unprecedented platform for modeling APOE genotype-dependent AD pathology at cellular resolution.
Research Question
Can APOE isoform-specific Alzheimer's disease pathology be faithfully recapitulated using isogenic iPSC-derived brain organoids?