ADVANCES IN THE MOLECULAR IMAGING OF ALZHEIMER'S DISEASE: NEUROBIOLOGICAL MECHANISMS OF DISEASE AND NEUROPSYCHIATRIC SYMPTOMS

The pathogenesis of Alzheimer's disease (AD) remains elusive. The observed accumulations of beta amyloid and phosphorylated tau protein aggregates are thought to play key roles in initiating or propagating the disease. However, other processes including changes in synaptic proteins, neurotransmitter loss, inflammation and cerebrovascular disease have been suggested as important etiologies as well. Importantly, the recent, unprecedented advancements of positron emission tomography (PET) radiotracer chemistry allow investigations into molecular changes associated with AD. Until recently, much of what is known about AD pathology has been learned from post mortem studies and animal models. The advancements of PET imaging allows quantitative in vivo measurements of specific proteins within many brain regions. Because the manifestations of AD are heterogeneous. The use of PET imaging can be used to improve the understanding of diverse symptoms. For example, a majority of individuals experience neuropsychiatric symptoms during the disease process, but the onset and composition of these symptoms vary widely. Molecular imaging using PET allows us to study neurobiological processes both early in the disease process and longitudinally. PET imaging can be used in concert with other imaging modalities such as MRI, as well as assessments of cognition and neuropsychiatric symptoms to investigate the molecular underpinnings of AD. It is of great importance for clinicians to learn about these innovative and translational tools which will ultimately lead to the identification of disease biomarkers and therapeutic targets. The goal of this session is to illustrate the importance of in vivo molecular imaging in the study of AD with a specific emphasis on PET. Dr. Adam Mecca (Chair) will present results of cross-sectional studies that investigate synaptic protein alterations in individuals with AD. These investigations utilize specific PET tracers to quantify synaptic density and metabotrophic glutamate receptor subtype 5 (mGluR5). Dr. Nancy Donovan will describe research that examines the relationships between cortical and subcortical brain amyloid quantified using PET, anxiety, and AD risk in cognitively normal older adults. Dr. Jennifer Gatchel will present work on the association between depressive symptoms and in vivo cerebral tau and amyloid measurements. Dr. Gwenn Smith will describe the role of serotonin (5-HT), tau and amyloid b in cognitive decline in individuals with mild cognitive impairment and normal cognition. Finally, Dr. Donovan (Discussant) will lead the speakers in a panel discussion, along with Q&A involving session attendees.