Neuroimmunology

The neuroimmunology group focuses on the role of neuroinflammation in the pathogenesis of Alzheimer´s disease (AD) and in immune-based therapeutic strategies such as immunotherapy against the amyloid-β (Aβ) protein.

Resident microglia but also peripheral macrophages are attracted to and surround Aβ deposits in AD brain. These cells have been suggested to remove amyloid fibrils in response to Aβ-immunisation. However, despite their therapeutic potential, various aspects of their reactive kinetics and role in amyloid plaque homeostasis and AD pathogenesis remain hypothetical. Through use of in-vivo imaging of amyloid precursor protein (APP) transgenic mice that have been crossed with Iba1-eGFP mice, we study the role of GFP-positive microglia to amyloid plaque formation. The role of invading peripheral immune cells is studied by reconstitution of such mice with bone marrow from Actb-eCYP transgenic mice.

The role of microglia and macrophages in AD is further characterized by using transgenic mice in which microglia can selectively be ablated (CD11b-HSVTK mice). Such mice are crossed with APP transgenic mice and thus allow us to investigate the effect of microglia ablation on cerebral amyloid deposition and removal.

APP transgenic mice deficient in various immune-associated molecules or cell types are used to evaluate the consequences of immune system manipulations on AD pathogenesis. To this end we will reconstitute such immune-deficient mice with human stem cells to create APP transgenic mice with a human immune system. Such transgenic mouse models are well-suited for developing specific therapeutic strategies to enhance the beneficial (or silence the detrimental) components of neuroinflammatory reactions.

Recent publications

Grathwohl SA, Kalin RE, Bolmont T, Prokop S, Winkelmann G, Kaeser SA, Odenthal J, Radde R, Eldh T, Gandy S, Aguzzi A, Staufenbiel M, Mathews PM, Wolburg H, Heppner FL, Jucker M (2009) Formation and maintenance of Alzheimer's disease beta-amyloid plaques in theabsence of microglia. Nat Neurosci 12:1361-3 (Abstract)