Assessment of circulating apoE4 levels from dried blood spot samples in a large survey setting.

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele is associated with high risk for Alzheimer's disease. It is unclear whether individual levels of the circulating apoE4 protein in ε4 carriers confer additional risk. Measuring apoE4 protein levels from dried blood spots (DBS) has the potential to provide information on genetic status as well as circulating levels and to include these measures in large survey settings. METHODS: We developed a multiplex immunoassay to detect apoE4 protein levels in DBS from 15,974 participants, aged 50+ from Wave 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE). RESULTS: The apoE4 protein signal was presented in two separable distributions. One distribution corresponded to carriers of at least one copy of the ε4 allele. Fieldwork cofounders affected protein levels but did not explain individual differences. DISCUSSION: Future research should investigate how genotype and apoE4 level interact with lifestyle and other variables to impact cognitive aging.

Arbitration between model-free and model-based control is not affected by transient changes in tonic serotonin levels.

BACKGROUND: Serotonin has been suggested to modulate decision-making by influencing the arbitration between model-based and model-free control. Disruptions in these control mechanisms are involved in mental disorders such as drug dependence or obsessive-compulsive disorder. While previous reports indicate that lower brain serotonin levels reduce model-based control, it remains unknown whether increases in serotonergic availability might thus increase model-based control. Moreover, the mediating neural mechanisms have not been studied yet. AIM: The first aim of this study was to investigate whether increased/decreased tonic serotonin levels affect the arbitration between model-free and model-based control. Second, we aimed to identify the underlying neural processes. METHODS: We employed a sequential two-stage Markov decision-task and measured brain responses during functional magnetic resonance imaging in 98 participants in a randomized, double-blind cross-over within-subject design. To investigate the influence of serotonin on the balance between model-free and model-based control, we used a tryptophan intervention with three intervention levels (loading, balanced, depletion). We hypothesized that model-based behaviour would increase with higher serotonin levels. RESULTS: We found evidence that neither model-free nor model-based control were affected by changes in tonic serotonin levels. Furthermore, our tryptophan intervention did not elicit relevant changes in Blood-Oxygenation-Level Dependent activity.