The effect of education on ATN biomarkers of Alzheimer’s disease according to the presence of APOE4

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Abstract Background As a proxy of cognitive reserve, education is known to have a protective effect against the cognitive decline in Alzheimer’s disease. It is explained that those who have higher education would resist pathologic burdens through other mechanisms such as changes of functional networks of the brain. However, it is not well known whether there is an association between education and the pathologic burden. APOE is the important genetic risk factor, and the presence of the ε4 allele is associated with biomarkers. This study aimed to evaluate the association between education and ATN biomarkers in Alzheimer’s disease according to the presence of APOE4. Method We analyzed 1,076 Alzheimer’s Disease Neuroimaging Initiative participants’ data (336 cognitively normal (CN), 279 early aMCI, 279 late aMCI, 182 AD). The values of CSF amyloid β1‐42, CSF phosphorylated Tau (p‐Tau), and 18F‐fluorodeoxyglucose‐positron emission tomography (FDG PET) brain metabolism were used as ATN biomarkers. We analyzed the association between education and ATN biomarkers in each group, according to the presence of APOE ε4 allele, using a multiple linear regression model after controlling age and sex. Result Higher education was related to lower CSF p‐Tau in the early aMCI group only when APOE4 was positive (β = ‐1.3, p = 0.013). Other than the early aMCI group, we could not find any association between education and ATN biomarkers. Conclusion This finding suggests that education could have a protective effect on the pathologic tau burden in the presence of APOE4, especially at the early aMCI stage.

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