Fourth, to our knowledge, this is the first population-based prospective study to have examined interactions and associations among 3 primary constructs (APOE4 carrier status, blood-based neurodegenerative biomarkers, and measures of cognitive decline), notably investigating 3 serum neurodegenerative biomarkers and the modifying interactions of APOE4 status with them in the same study, thus translating and validating animal findings in human samples. Here, APOE is linked to Mental deterioration.