Highlight
– The APOE ε4 allele (rs429358) is significantly associated with reduced survival in patients with Parkinson’s disease (PD), independent of the presence of dementia.
– Time-to-event genome-wide analysis in a large cohort of White European PD patients identified APOE ε4 as a genetic determinant negatively impacting patient survival.
– Cellular models expressing APOE ε4 under PD-related stress conditions demonstrated reduced cell viability, mitochondrial dysfunction, increased DNA damage, and activation of endoplasmic reticulum (ER) stress via the PERK pathway.
– These findings reveal biological mechanisms through which APOE ε4 may influence PD progression and patient mortality beyond cognitive decline.
