Human cortical organoids to study Alzheimer´s disease 

Human cortical organoids to study Alzheimer´s disease 

Human brain organoids have ushered in a new era for modeling neurodegenerative diseases. Our research focuses on elucidating the role of oligodendrocytes and myelin in the onset and progression of Alzheimer’s disease (AD). We hypothesize that age-related myelin dysfunction impairs neural connectivity and disrupts metabolic support to neurons and glia, thereby contributing to AD pathogenesis. Challenging conventional views, we propose that restoring myelin integrity, modulating myelin lipid catabolism, or supplementing myelin-derived fatty acids may mitigate neuropathological features and functional deficits in AD. To investigate this, we generate cortical organoids from induced pluripotent stem cells (iPSCs) derived from patients with both sporadic and familial forms of AD. These organoids recapitulate key hallmarks of AD pathology, which we analyze using high-resolution microscopy, immunohistochemistry, and electrophysiology. Preliminary findings indicate that myelin-derived fatty acids can partially reverse AD-associated pathology.