Abstract
-
Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, yet current
therapeutic treatments are inadequate due to a complex disease pathogenesis. The plant polyphenol
apigenin has been shown to have anti-inflammatory and neuroprotective properties in a number of
cell and animal models; however a comprehensive assessment has not been performed in a human
model of AD. Here we have used a human induced pluripotent stem cell (iPSC) model of familial and
sporadic AD, in addition to healthy controls, to assess the neuroprotective activity of apigenin. The
iPSC-derived AD neurons demonstrated a hyper-excitable calcium signalling phenotype, elevated levels
of nitrite, increased cytotoxicity and apoptosis, reduced neurite length and increased susceptibility to
inflammatory stress challenge from activated murine microglia, in comparison to control neurons. We
identified that apigenin has potent anti-inflammatory properties with the ability to protect neurites
and cell viability by promoting a global down-regulation of cytokine and nitric oxide (NO) release in
inflammatory cells. In addition, we show that apigenin is able to protect iPSC-derived AD neurons
via multiple means by reducing the frequency of spontaneous Ca2+ signals and significantly reducing
caspase-3/7 mediated apoptosis. These data demonstrate the broad neuroprotective action of apigenin
against AD pathogenesis in a human disease model.