Background:
Alzheimer's disease (AD) is characterized by presenting a complex pathology,
not fully resolved yet. This fact, together with the lack of reliable models, has
impeded the development of effective therapies. Recently, several studies have
shown that functional glial cell defects have a key role in the pathology of AD.
However, this glial dysfunction, currently, cannot be correctly modeled using
the available animal models, so we hypothesized that cells derived from
Alzheimer's patients can serve as a better platform for studying the disease. In
this sense, human pluripotent stem cells (hPSC) allow the generation of
different types of neural cells, which can be used for disease modeling,
identification of new targets and drugs development.
Methods:
We have a collection of hiPSCs derived from patients with sporadic forms of
AD. We have differentiated these cells towards neural lineage to obtain neurons
and astrocytes. For the generation of oligodendrocytes (OLs), we have
developed a fast and robust protocol to generate mature OLs in just 22 days.
Results:
We have generated neural precursors from all the lines tested. In the case of
OLs, the cells generated resemble primary OLs and can myelinate neurons in
vivo and in vitro using a screening compatible platform. This platform is being
transferred for the generation of the other glial cells.
Conclusions:
This methodology can be used to elucidate the pathogenic pathways associated
with neurodegeneration and to identify new therapeutic targets susceptible to
modulation, contributing to the development of new effective drugs against AD.
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