Molecular Imaging in Alzheimer's Disease: Linking pathologic, neurotransmitter, synaptic and clinical findings relevant to geriatric psychiatry

The pathogenesis of Alzheimer's disease (AD) remains elusive and rests predominantly on the observed accumulations of amyloid beta and phosphorylated tau protein aggregates that 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. Furthermore, the manifestations of AD are heterogeneous. A majority of individuals experience neuropsychiatric symptoms during the disease process, but the onset and composition of these symptoms vary widely. Until recently, much of what is known about AD pathology has been learned from post mortem studies and animal models. The advancements of positron emission tomography (PET) imaging allow in vivo investigations into molecular changes associated with AD. Molecular imaging using PET allows us to study multiple biomarkers both early in the disease process and longitudinally. PET imaging can be used in concert with other imaging modalities, such as MRI, and with 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 will present results of cross-sectional studies that investigate synaptic protein alterations in AD, and the association between synaptic density and tau accumulation. These investigations utilize specific PET tracers to quantify synaptic density and tau. Dr. Gwenn Smith will describe longitudinal changes in serotonin (5-HT), tau and amyloid in relationship to cognitive decline and neuropsychiatric symptoms in individuals with mild cognitive impairment and normal cognition. Dr. Jennifer Gatchel will present work describing associations between subjective cognitive and depressive symptoms and in vivo cerebral tau and amyloid measurements. Dr. Nancy Donovan (Chair) will describe a longitudinal study examining the combined effects of widowhood status and PET-derived amyloid measures on cognitive outcomes in cognitively normal older adults. Finally, Dr. Gatchel (Discussant) will lead the speakers in a panel discussion, along with Q&A involving session attendees.