β-amyloid 1-42 oligomers impair function of human embryonic stem cell-derived forebrain cholinergic neuronsβ-amyloid 1-42寡聚物损害人类胚胎干细胞功能前脑胆碱能神经元.pdf

b-Amyloid 1-42 Oligomers Impair Function of Human Embryonic Stem Cell-Derived Forebrain Cholinergic Neurons 1 ˜ 2 ¨ 3 1 3 Linn Wicklund , Richardson N. Leao , Anne-Marie Stromberg , Malahat Mousavi , Outi Hovatta , Agneta 1,4 1 Nordberg , Amelia Marutle * 1 Department of Neurobiology, Care Sciences and Society, Division of Alzheimer Neurobiology, Karolinska Institutet, Stockholm, Sweden, 2 Department of Neuroscience, Neuronal Oscillation Laboratory, Karolinska Institutet, Stockholm, Sweden, 3 Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden, 4 Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden Abstract Cognitive impairment in Alzheimer’s disease (AD) patients 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 human brain, and the stimulation of regenerative processes in the CNS is an attractive prospect for neuroreplacement therapy in neurodegenerative diseases such as AD. Currently, it is still not clear how the pathophysiological environment in the AD 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 neurotoxic effects on progenitor cell populations have been reported. In this study, we treated pluripotent human embryonic stem (hES) ce