SPON1 is associated with amyloid-β and APOE ϵ4-related cognitive decline in cognitively normal adults

Background: Genetic variation in Spondin-1, specifically rs11023139, has been associated with reduced rates of cognitive decline in individuals with Alzheimer's disease. Objective: The aim of this study was to assess whether the association was present in cognitively normal older adults. Methods: Longitudinal cognitive decline was investigated using linear mixed modelling in a cohort of 590 cognitively normal older adults enrolled in the Australian Imaging, Biomarkers and Lifestyle Study. Results: No independent effect of Spondin-1 rs11023139 on cognitive decline was observed. However, significant associations were observed for the interaction between Apolipoprotein E (APOE) ϵ4 and rs11023139 in individuals with high amyloid-β burden. APOE ϵ4/rs11023139-A carriers declined significantly faster than APOE ϵ4/rs11023139-G-G carriers in measures of global cognition (p=0.011) and verbal episodic memory (p=0.020). Conclusion: These results suggest that carriage of the Spondin-1 rs11023139-A allele significantly contributes to a worsening of cognitive performance in APOE ϵ4 cognitively normal older adults with a high neocortical amyloid-β burden.