ApoE4 binding in dried blood spots is associated with lower cognition in a population‐based sample of 50+ non‐demented adults

Abstract Background The ApoE ε4 allele is a major risk factor for late‐onset Alzheimer’s disease and cognitive decline in ageing (Corder et al., 1993) but the role of the circulating ApoE4 protein on cognition is still under debate (Simon et al., 2012; Wang et al., 2014). Here, we report the distribution of circulating ApoE4 protein, assessed from dried blood spots, in a large population‐based sample. Preliminary analyses examined its associations with cognition and lifestyle factors. Method Measures of memory (word recall), verbal fluency and dried blood spot samples were collected during the 6 th Wave of the Survey of Health, Ageing and Retirement in Europe ‐ SHARE (N = 12,531, 50y and over, 59.3% females). An assay to specifically bind to the ApoE4 protein in dried blood spots was developed. Data driven cut‐offs were tested to divide the ApoE4 binding distributions in specific and non‐specific types. Next, multiple linear regressions were used to test the association between ApoE4 binding type and cognition. Models were adjusted for available demographic, lifestyle and health‐related variables. Interaction terms between age and ApoE4 binding type were created. Finally, specific binding levels were used as a continuous outcome to assess whether they were associated with demographic, health or lifestyle variables. Result A cut‐off of 50.000 pg/mL was chosen to separate the distributions of specific (28.4%) vs. non‐specific (71.6%) ApoE4 binding (Fig. 1). Belonging to the specific binding group had a significant negative effect on word recall (ps < 0.001) but not on verbal fluency. Interaction effects between age and specific ApoE4 binding were observed in all models, with the effect of specific ApoE4 binding on cognition magnified for adults aged 75‐84y (Fig. 2A, 2B and 2C). Finally, higher BMI, female sex and hypertension (all ps < 0.05) were predictors of higher levels of specific ApoE4 binding. Conclusion Specific and non‐specific binding to the ApoE4 protein, assessed in dried blood spots, followed known population frequencies of ApoE ε4 allele (Gerdes, 2003). Specific ApoE4 binding was associated with worse cognitive performance. Higher specific ApoE4 levels were associated with female sex and cardiovascular factors.