Pathogenic SORL1 variants in Alzheimer’s disease (SORLA - FIX)
The SORLA protein is a neuronal sorting receptor encoded by the SORL1 gene. Functional SORLA keeps the levels of Amyloid-β in the brain in a healthy balance regulating APP processing into Amyloid-β, and by binding excess Amyloid-β to target it for lysosomal degradation. In the past two-three years it has become clear that heterozygous, damaging variants in the SORL1 gene are associated with and possibly causative for AD. Furthermore, the load of pathogenic and risk-increasing SORL1 variants in AD patients is large, which suggests that it is imperative to invest in the identification of those at risk to become affected with SORL1-associated AD, and the selective treatment of affected individuals. In this proposal we have created a collaboration of international investigators who are highly capable of answering the open questions regarding SORL1 variant pathogenicity and protein functions. Within this synergy of expertise, we will generate a working-pipeline to assess SORL1 variant pathogenicity, allowing the accurate diagnosis of patients with SORL1-associated AD and we will invest in the identification of selective SORL1-boosting or SORL1-fixing treatments applicable to individuals affected by compromised SORLA function.
Sustainable Development Goals
Masaryk University is committed to the UN Sustainable Development Goals, which aim to improve the conditions and quality of life on our planet by 2030.
Total number of publications: 2