Effect of spread of tau on functional connectivity patterns in the preclinical and prodromal stage of Alzheimer disease

Dementia is a worldwide growing problem. It is estimated that there will be around 130 million cases of Alzheimer’s disease (AD) by 2050, mainly due to ageing of the baby boom generation. Cognition results from an optimal cooperation of local information processing and interregional integration. This communication can be approximated by the measurement of the functional connectivity, quantified with graph analysis. Neurofibrillary tangles (NFTs), consisting of hyperphosphorylated tau, correlate with neurodegeneration and the severity of dementia. The relation between global graph characteristics derived from EEG and tau load will be examined in cognitively intact individuals in a preclinical stage of AD and in patients with a prodromal and early dementia stage due to AD, as well as amyloid-negative controls. Tau load will be measured using 18F-MK-6240 PET. EEG is a non-invasive and less expensive technique that may be able to detect neurodegeneration before actual tissue loss or behavioural symptoms appear and could therefore become a method to diagnose AD in an early stage. High-density resting-state EEG will be measured under two conditions, eyes open and eyes closed, and analysed in sensor space. We will also measure resting state connectivity based on fMRI. This project will provide novel insight into how tau spread affects functional networks in the brain in the preclinical and early clinical stages of AD.