Alzheimer's disease (AD) is a complex neurodegenerative condition that is
clinically characterized by impaired cognitive functions. The major morphologically
observed lesion of AD encompasses the accumulation of extracellular amyloid
aggregates (plaques) formed of amyloid-β (Aβ) protein and of intracellular
neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein. According to the
currently accepted amyloid cascade hypothesis, the major induction factor underlying
the loss of cholinergic neurons in the cortex and hippocampus is the pathological
accumulation of a smaller protein fragments known as amyloid-β which in turn is
derived from a larger membrane protein called amyloid precursor protein (APP). Based on this hypothesis, several diagnostic and drug-based therapeutic interventions were
suggested, mostly targeting amyloid-β and hyperphosphorylated Tau proteins. Several
data have emerged that might indicate the inconsistency of the amyloid cascade
hypothesis. Moreover, due to the purely palliative nature of AD drugs used so far, new
stem cell-based therapy has been suggested as a promising potential therapeutic
approach. Several cell sources have been used, such as embryonic stem cells, neural
stem cells, mesenchymal stem cells, and induced pluripotent stem cells. While this
suite of cell-based trials has shown promising results in preclinical paradigms,
stumbling blocks still exist in the current treatment regimens. The present review
highlights the recent perspective that argues against the long standing amyloid cascade
hypothesis as well as the major efforts in the experimental application of stem cellbased
therapies used as treatment options for AD, and discusses the major impediments
against their successful translation into clinical.
