Poster: Stem cells in the Hunter Valley, ASSCR 2015

Finally a chance to demonstrate our stem cell advances at the 8th meeting of the Australasian Society for Stem Cell Research: 8 & 10th November in the Hunter Valley (NSW). (Poster 223, ASSCR). Come by to find out about differentiation of basal forebrain cholinergic neurons!


Cholinergic neurons differentiated from sporadic Alzheimer’s disease patient stem cells show
disease-relevant tau pathology

Engel M., Sanz Muñoz S., Ooi L.,

Alzheimer’s disease (AD) is a complex neurodegenerative disorder, characterized by extracellular plaques consisting primarily of amyloid β and intracellular tangles consisting primarily of tau. Recent work with transgenic AD animal models suggests that AD-characteristic tau pathology occurs prior to the onset of behavioural dysfunction. Tau pathology development appears to differ between brain regions in these AD mouse models. Analysis of post-mortem AD patient tissue indicates that cholinergic neurons in frontal cortex areas are affected early in the progression of AD, prior to dopaminergic neurons. However, the involvement and contribution of different neuronal cell types in the tau progression remains unclear.

Here we assessed whether expression levels of intracellular tau differ between cholinergic and dopaminergic neurons of individuals with sporadic AD (SAD) in comparison to neurons from healthy individuals. We differentiated frontal cortex cholinergic and midbrain dopaminergic neurons from induced pluripotent stem cells and quantified total tau levels as well as AD-relevant pathogenic tau. We found that the ratio of total tau to AD-relevant pathogenic tau varies between the cell types and between diagnoses. Cholinergic neurons from SAD patients had a higher ratio of pathogenic tau (Alz50) vs total tau (Tau-13) compared to neurons from healthy individuals. Furthermore, the ratio of Alz50 vs Tau-13 was higher in cholinergic than dopaminergic neurons from SAD patients. These preliminary findings indicate that tau pathophysiology differs between neuronal subtypes. The heightened level of pathogenic tau in cholinergic neurons suggests an inherent difference in tau processing in this cell type. Furthermore, our results suggest that human iPSC-derived neural cultures provide a suitable system to study cell type specific AD mechanisms, specifically their contribution to the tau pathophysiology. In current experiments we are exploring the temporal progression of the variation in cell-type specific tau pathology and its consequence on dendrite morphology and cell viability.

Forebrain Cholinergic neurons differentiated from human stem cells

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