Translational Neurodegeneration

We use induced pluripotent stem cells, iPSCs (Fig. 1A, B), for modelling and understanding human brain diseases and for regenerative therapies with a focus on Alzheimer’s Disease (AD) and stroke, respectively.

AD is the most common type of dementia with the apolipoprotein E4 (APOE4) allele as major genetic risk factor. Using either AD patient-derived iPSCs or isogenic cells that differ only in their AD risk genes, we aim to better understand AD pathomechanisms in differentiated human cortical neurons (Fig 1C, D) and astrocytes (Fig. 1E, F).

Stroke causes a permanent disability to five million people each year. This is largely due to the lack of effective medical treatment that promotes long-term recovery. Therefore, we are developing a next-generation regenerative therapy for stroke based on transplantation of iPSC-derived cells (Fig. 1G, H) in collaboration with Dr. Ruslan Rust.

 

Tackenberg Research Illustration
Tackenberg Research Illustration
Fig1

A: Phase contrast microscopy of an iPSC colony. B: iPCS colony staining for pluripotency markers Nanog and Tra-1-60. C, D: Induced neurons from iPSCs at DIV21 are positive for the neuronal markers tau and Map2 and display PSD-95-positive postsynaptic as well as synapsin-positive presynapti punctae. E, F: iAstrocytes express astrocytic markers S100β, GJA1 (Connexin 43) and GFAP at DIV44. G, H: Neural progenitor cells (NPCs), derived from iPSCs, express typical marker proteins Pax6, Sox1, Nestin but not pluripotency marker Oct4. These are used for transplantation studies. Images are taken from de Leeuw at al., 2022, Stem Cell Reports; Rust et al., 2022, Journal of Translational Medicine; de Leeuw and Tackenberg, 2019, Translational Neurodegeneration; and Birnbaum et al., 2018, Stem Cell Research.

Funding:

Swiss Commission for Technology and Innovation (CTI); Novartis Foundation for Medical-Biological Research; University of Zurich; Olga Mayenfisch Foundation; Neuroscience Center Zurich; Betty & David Koetser Foundation for Brain Research; Dr. Wilhelm Hurka Foundation; German Research Foundation; Swiss 3R Competence Center