Pros and Cons of Human Brain Organoids to Study Alzheimer’s Disease

There is increasing pressure for researchers to reduce their reliance on animals, particularly in early-stage research. The main reason for that change arises from the different biological behavior of humans that leads to frequent failure of translating data from bench to bed. The advent of organoid technology ten years ago, along with the feasibility of obtaining brain organoids in most laboratories, has created considerable expectations not exempting frustration. In this review, we make a critical appraisal of the advantages and limitations of studying Alzheimer´s disease in brain cortical organoids derived from inducible pluripotent stem cells (iPSCs). While dealing with human neurons and glia in 3D poses a tremendous advantage versus murine brain cells, organoids typically lack microglia, blood vessels, immune interactions as well as proper CNS neuropil. In turn, they have relatively few oligodendrocytes and low myelination. In addition, lengthy procedures to get proper mature organoids constitute an additional limitation that may also affect the native biological properties of neurons and glia. We conclude that human brain organoids, while popular and useful, remain a model that needs further refinement before bringing substantial value to study Alzheimer´s disease.