| dc.description.abstract | The Apolipoprotein E (ApoE) 4 gene is the strongest genetic risk factor for late-onset Alzheimer’s Disease (AD). The ApoE 3 is the most common allele, but the ApoE 4 allele, occurring in 15% of the population is found in 60% of patients suffering from AD. The aim of this study was to culture astrocytes expressing ApoE 3 and 4 with neurons that show early AD pathology. Early AD pathology is seen in the medial temporal lobe, in the lateral entorhinal cortex (LEC) and the surrounding hippocampal regions. The neurons used were adult mice LEC neurons from both AD and non-AD mouse models, as well as commercially available hippocampal neurons. The astrocytes are from mice that transgenically express humanized ApoE 3, ApoE 4, or have murine ApoE knocked out.
The primary adult LEC neurons did not survive on these ApoE astrocytes, in these initial experiments. More trials are needed to optimize protocol for these cells, as they are very fragile. The commercially available hippocampal neurons did survive on the ApoE astrocytes. The results indicate that ApoE is important for neuron survival, as the ApoE knockout astrocyte cultures had the lowest number of neurons compared to the other cultures. Electrophysiology data were also gathered from these cells using CMOS microelectrode arrays. These novel data appeared to indicate that the different astrocyte conditions promote different neuronal activity. The ApoE 4 and ApoE knockout cultures appeared to show less synchronous bursting than the ApoE 3 and hippocampal astrocyte (control) culture. The ApoE 4 culture showed lower average firing rates and bursting rates than all other cultures, and the ApoE knockout culture had the highest firing rates and more bursts with more spikes, than other cultures. | |