LEGT_EGG is an academic research-group dedicated to understand fundamental mechanisms that operate in normal processes of learning and memory that become defective during ageing in Alzheimer's disease (AD). LEGT_EGG main technical activities are situated in the generation and in depth phenotyping of transgenic mice by behavioural, biochemical, pathological analysis.

LEGT_EGG has generated and characterized over the last 15 years relevant transgenic mouse models that recapitulate, separately and combined in bi-genic models, the amyloid and tau-pathology as major pathological hallmarks of AD. These and additional single and bi-genic mouse models are highly informative for the essential and modulating actions of the proteinases and kinases that process the amyloid precursor protein (APP) and protein tau, i.e. the so-called "secretases" ADAM10, BACE, PS1 and the kinases GSK-3b and cdk5/p35.

The transgenic mouse models are validated for diagnostic and therapeutic applications, either in-house but also in numerous academic and industrial collaborations. These activities gave rise to our KULeuven spin-off reMYND nv (° 2002) in close collaboration with the yeast cell-biology research-group of Functional Biology in the faculty of Sciences (head: Prof. Dr. J. Winderickx). The main activity of reMYND as a drug-developing company is focused on protein tau and tauopathy.

Prof. Van Leuven is also co-founder of the biotech company AC-Immune (Lausanne) focused on the amyloid pathology as therapeutic target by chemical (amyloid-breakers) and immunochemical (active and passive vaccination) routes.

Most recently, the group is oriented nearly completely towards understanding the physiology and pathology of protein tau, continuing previous work on wild-type and mutant tau.4R and Tau.P301L mouse and yeast models. The major underlying reasons for the re-orientation are our newest findings of the direct involvement of GSK3 in linking amyloid to tau in vivo, establishing it as the major tau-kinase that is activated by amyloid (Terwel et al, 2008).

Moreover, the newly developed adeno-associated viral models (AAV-models) (in co-laboration with S.Kügler, Göttingen) demonstrate in vivo that not amyloid but phosphorylated tau is neurotoxic !

Our working hypothesis for most of our projects and studies thereby becomes:
amyloid is the trigger, phosho-tau the executer and GSK3 kinases the major mediators between both pathologies .