The impact of early medial temporal lobe Tau in human cognitive aging

Memory decline is a common complaint among older individuals. Interestingly, the pathological changes of Alzheimer’s disease (AD) begin years before clinical symptoms of dementia are noticeable, and may contribute to decline in memory among putatively ‘healthy’ older individuals that have performance in the normal range. Positron emission tomography (PET) allows the visualization of early AD pathology. In particular, the abnormal aggregation of the Tau protein is a hallmark pathological feature of AD dementia, and is also common among older normal adults. Interestingly, the accumulation of the Tau protein begins in the medial temporal lobe, a brain region that is essential for the formation of new memories. By combining PET imaging with high-resolution magnetic resonance imaging (MRI) to measure the structure and function of the medial temporal lobe, we can understand how this early AD pathology influences memory in healthy older individuals and whether these early changes can predict who is most at risk for AD dementia in the future. Given the failure of multiple clinical trials in symptomatic AD dementia patients, there is hope that targeting the disease as early as possible, even before symptoms are present, will be a successful strategy against AD.