P1‐410: Multitracer PET studies in kindreds with early‐onset familial Alzheimer gene mutations

Abstract

Attempts to develop markers for the earliest possible diagnosis of Alzheimer's disease (AD) have led to an increasing impact of studies in subjects carrying autosomal dominantly inherited genes that lead to the rare early-onset familial form of Alzheimer's disease (eoFAD). These subjects are predestined to develop AD, which makes studies in presymptomatic subjects an unique possibility to study the earliest pathological changes in the brain in the process of developing AD and following them a way to depict the disease time course. Neuroimaging by means of positron emission tomography (PET) has shown that cerebral changes in glucose metabolism and accumulation of fibrillar amyloid plaques are early events in the disease process. Few PET studies have though tried to investigate the role of neuroinflammation as a pathological hallmark of AD and thereby mostly focused on the activation of microglia. As a starting point in a series of longitudinal investigations we recently published longitudinal data on presenilin 1 (PS1) mutation carriers, who were in average about twenty years before the expected onset of the disease (Schöll et al., Neurobiology of Aging, 2009). 18F-Fluorodeoxyglucose (FDG) PET revealed thalamic glucose hypometabolism and an 11C-PIB PET scan in one symptomatic mutation carrier high PIB uptake in AD typical brain regions with eminently elevated levels in striatum. In the current longitudinal study, we enrolled presymptomatic and symptomatic members of different Swedish families harboring mutations in the PS1 gene and the ‘Swedish’ and the ‘Arctic’ APP gene mutations. We use the PET tracers 18F-FDG to investigate cerebral glucose metabolism, 11C-PIB for cerebral amyloid load measurements, and 11C-Deprenyl to visualize astrocytosis as a component of neuroinflammatory processes. The acquired PET data will be set in relationship to neuropsychological test results and the interrelation between different tracers and different mutations examined. Application of multiple PET tracers in members of families harboring eoFAD mutations will provide important information about the time course and properties of AD pathology and about differences between eoFAD mutations.