Alzheimer's Disease
Alzheimer’s disease (AD) is a common neurodegenerative disorder characterised by extensive loss of hippocampal and cortical volume associated with deposition of extracellular amyloid “plaques” and intracellular tau “tangles”. Damage to synapses and neurons within the hippocampus and associated structures is thought to underlie the main symptoms of AD, namely memory loss.
In our lab, we have developed a novel organotypic hippocampal slice culture (OHSC) model to study aspects of AD. By culturing thin sections of murine hippocampus (which overexpress human amyloid precursor protein (APP) containing familial AD associated mutations) in vitro we can observe progressive AD-related changes in this brain region. OHSCs are more representative of the in vivo brain architecture and resident cell types than more typically used primary neuronal cultures, but gain the in vitro advantages of accessibility to observation and pharmacological manipulation that is difficult to achieve in vivo. In our lab, we are using these cultures to model both familial and sporadic AD with our main focus being on understanding factors controlling synapse loss.