Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSC) have a 
potential therapeutic role in the treatment of neurological disorders, but their 
current clinical usage and mechanism of action has yet to be ascertained in 
Alzheimer's disease (AD). Here we report that hUCB-MSC transplantation into 
amyloid precursor protein (APP) and presenilin1 (PS1) double-transgenic mice 
significantly improved spatial learning and memory decline. Furthermore, 
amyloid-β peptide (Aβ) deposition, β-secretase 1 (BACE-1) levels, and tau 
hyperphosphorylation were dramatically reduced in hUCB-MSC transplanted APP/PS1 
mice. Interestingly, these effects were associated with reversal of 
disease-associated microglial neuroinflammation, as evidenced by decreased 
microglia-induced proinflammatory cytokines, elevated alternatively activated 
microglia, and increased anti-inflammatory cytokines. These findings lead us to 
suggest that hUCB-MSC produced their sustained neuroprotective effect by 
inducing a feed-forward loop involving alternative activation of microglial 
neuroinflammation, thereby ameliorating disease pathophysiology and reversing 
the cognitive decline associated with Aβ deposition in AD mice.