Pathophysiology of Down's syndrome and rare dose-effect diseases causing intellectual disabilities (ID) or autism spectrum disorders (ASD) and other comorbidities
Team Leader : Yann HERAULT
Department : Translational medecine and neurogenetics
Neurons and synapses
Alzheimer’s disease (AD) is a major neurodegenerative disorder affecting the human population in two principal forms: Early Onset AD (EOAD) mainly due to rare genetic variants, affecting the function of APP, PSEN1, or PSEN2; and Late Onset AD (LOAD) which involves very rare or more common variants of various genes (for example APOE, TREM2, BIN1, CLU or CR1). We have investigated BIN1 overdosage in LOAD and propose a model for its interaction with TAU/MAPT (Sartori et al., 2019).
Now our interest is centered on AD being a common co-morbidity in Trisomy 21 or Down Syndrome (DS), the location of the APP gene on human chromosome 21 (Hsa21), lends DS as a model of the amyloid theory of AD. The project will investigate the common mechanisms of dementia in Trisomy 21 and AD, using preclinical approaches. Bridging natural history of AD in DS, developing cellular and animal models, exploring omics and biomarkers, and including bioinformatics modelling, we will improve our understanding of the mechanisms and molecular pathways underlying the pathophysiology of both diseases. Our research will result in novel innovations in the development of treatment for Dementia in DS and AD.