-amyloid 1-42 oligomers impair function of hu XXXX mbryonic stem cell-derived forebrain cholinergic neurons.

@entity1 @entity73 @entity4150 @entity179 @entity460 @entity195 @entity2359
@entity73 in @entity195 ( @entity195 ) @entity1 is associated with a decline in the levels of growth factors, impairment of axonal transport and marked degeneration of basal forebrain cholinergic neurons (BFCNs). Neurogenesis persists in the adult @entity1 brain, and the stimulation of regenerative processes in the CNS is an attractive prospect for neuroreplacement therapy in @entity179 such as @entity195 . Currently, it is still not clear how the pathophysiological environment in the @entity195 brain affects stem cell biology. Previous studies investigating the effects of the b-amyloid (Ab) peptide on neurogenesis have been inconclusive, since both neurogenic and @entity2359 effects on progenitor cell populations have been reported. In this study, we treated pluripotent @entity1 embryonic stem (hES) cells with @entity4150 ( @entity4150 ) as well as with fibrillar and oligomeric Ab1-40 and Ab1-42 (nM-  M concentrations) and thereafter studied the differentiation in vitro during 28-35 days. The process applied real time quantitative PCR, immunocytochemistry as well as functional studies of intracellular @entity460 signaling. Treatment with @entity4150 promoted the differentiation into functionally mature BFCNs. In comparison to untreated cells, oligomeric Ab1-40 increased the number of functional neurons, whereas oligomeric Ab1-42 suppressed the number of functional neurons. Interestingly, oligomeric Ab exposure did not influence the number of hES cell-derived neurons compared with untreated cells, while in contrast fibrillar Ab1-40 and Ab1-42 induced gliogenesis. These findings indicate that Ab1-42 oligomers may impair the function of stem cell-derived neurons. We propose that it may be possible for future @entity195 therapies to promote the maturation of functional stem cell-derived neurons by altering the brain microenvironment with trophic support and by targeting different aggregation forms of Ab.
