The compromised activity of mutated β-glucocerebrosidase facilitates the accumulation and aggregation of α-synuclein and APOE-ε4 exacerbates the brain accumulation and subsequent deposition of amyloid-β.1 Interestingly, two recent studies indicated a novel role for APOE-ε4 in enhancing the α-synucleinopathy, and particularly the spread of Lewy body pathology,44,45 reinforcing the importance of APOE-ε4 as a potential therapeutic target in PDD. The gene discussed is SNCA; the disease is synucleinopathy.