Work package 3

In vitro and in vivo models of AD-related neuro-inflammation

 

In this work package 3 (WP3) in vivo experiments using animal models of Alzheimer’s disease (AD), human induced pluripotent stem cells (iPSC) and neuroimaging of patients to better understand neuroinflammatory responses in AD will be performed.

 

The first aim of WP3 is to use animal models of AD to understand the contribution of the activating/inhibiting innate immune receptors TREM2 and CD33 on disease progression and pathology.

 

The second aim of WP3 is to generate iPSCs with disease relevant genetic variants of TREM2 and CD33. A protocol for deriving human microglia/macrophages from iPSCs will be generated and the cells generated will be characterized to elucidate the function of the genetic risk genes TREM2 and CD33 for AD.

 

PET Centre
PET MRI Image

PET Centre (left), PET MRI Scan of the brain (right)
(images: Guy's and St. Thomas', KCL)

 

 

 

 

Macrophages with iPS-derived neurons

Co-culture of macrophages with iPS-derived neurons: red - macrophages, green - neurofilaments/neurons, blue - DNA/nuclei
(image: A. Shahraz, UKB)

 

 

 

The third aim of WP3 is to perform neuroimaging and analysis of cerebrospinal fluid (CSF) of patients with/without TREM2/CD33 disease risk variants to understand the contribution of these genes to AD disease progression and pathology and find new biomarkers for AD.

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This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115976. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA companies.

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This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115976. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA companies.