Lynne Krohn, PhD student at McGill University presents on REM Sleep Behavior Disorder genetics for early detection & subtyping of Parkinson disease and Kariem Ezzat, Research Scientist at Karolinska Institute discusses Heterogeneous Nucleation and Loss-Of-Function (HEN-LOF) Mechanisms in Amyloid Pathologies

Lynn presented that over 80% of REM sleep behavior disorder patients will convert to a synucleinopathy, primarily PD or dementia with Lewy bodies, within an average of 10-15 years. Understanding the genetics of RBD will aid in earlier detection of PD, subtyping of PD patients for more personalized treatment, and provide the possibility to genetically stratify RBD patients for clinical trials. In this talk I will highlight some important findings thus far, including a genetic distinction between PD subtypes at a key PD genetic risk locus, as well as potential genetic markers for rapid conversion from RBD to synucleinopathy.

Kariem presented that Amyloids are fibrillar protein aggregates associated with many neurodegenerative diseases. The pathogenicity of amyloids has long been considered to result from the toxic gain-of-function (GOF) of self-perpetuating protein-only species (prions). Here, we discuss the role of non-proteinaceous species such as microbial surfaces and lipid membranes in catalyzing amyloid formation via the independent mechanism of heterogeneous nucleation (HEN). Furthermore, we highlight that the loss of the native protein conformation due to amyloid transformation is accompanied by a loss-of-function (LOF) that contributes to amyloid toxicity. Based on these mechanistic insights, we argue that the amyloid phenomenon is not a protein-only phenomenon and that amyloids are incapable of holding or transmitting biological information. Additionally, we propose that soluble, non-aggregating forms of amyloidogenic proteins can be used for replacement therapy in neurodegenerative diseases.

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