Genetic Architecture of Synaptic Failure in Dementia with Lewy Bodies: From α-Synuclein Proteoforms to GBA1-Mediated Plasticity Deficits
It is argued that GBA1 loss-of-function and the resulting accumulation of glucosylceramide stabilise specific neurotoxic α-synuclein proteoforms, including soluble oligomers and self-templating conformational strains bearing defined post-translational modifications, and identifies the synapse as the most tractable node for early, disease-modifying intervention.