3D Alzheimer’s disease ‘brain on a chip’: generating amyloid accumulation and tau phosphorylation together with a neuro-immune response

Alzheimer’s dementia is a rapidly growing health issue for Australia and worldwide with an expected 136 million cases by 2050. The disease is characterised by accumulation of amyloid peptide and phosphorylated tau microtubule protein in the brain, together with an abnormal inflammatory response and neuronal cell death in affected brain regions. However, there is still little understanding of how these processes occur and why they are age-dependent. One of the major problems with trying to understand the disease and develop treatments is that there are no ideal cell models to allow detailed molecular and cellular studies.

To overcome this, we are developing a 3D Alzheimer’s disease ‘brain on a chip’ platform. We grow human neural stem cells and human brain macrophages in 3D cultures on an OrganoPlateTM culture platform (Mimetas, leaders in ‘organ on a chip’ technology). The aim is to generate amyloid accumulation and tau phosphorylation together with a neuro-immune response in the cultures more closely modelling the human Alzheimer’s brain (compared to 2D cultures of animal cells). These cultures can be used to understand how amyloid and tau accumulate, what role neuroinflammation has in the disease process, incorporation of patient cells, and enhance development of potential therapeutics that would normally only be examined in large scale animal studies.

Techniques will include neural stem cell and inflammatory cell culture, molecular studies (i.e. cell transfections), microscopy (confocal imaging) and protein analysis (western blot).

For more information on this group: http://www.qimrberghofer.edu.au/lab/cellular-molecular-neurodegeneration/