PET imaging in Down syndrome and Alzheimer's disease

Abstract Individuals with Down syndrome (DS) are at extremely high risk for Alzheimer's disease (AD), with the vast majority of adults with DS developing AD neuropathology by age 40. This is primarily due to the overproduction of amyloid-beta (Aβ) that begins early in life, caused by the presence of three copies of chromosome 21, each containing one copy of the Amyloid Precursor Protein (APP) gene. The accumulation of Aβ in the brain is hypothesized to initiate a “cascade” of biomarker changes, including the subsequent appearance of neurofibrillary tangles, glucose hypometabolism, and a decrease in hippocampal volume, resulting in cognitive and functional deficits and a diagnosis of dementia. This chapter provides a brief history of PET imaging and the radiotracers that have had a significant impact for measuring the three signature AD-related neuropathologies related to AD and provides an overview of the research utilizing PET imaging in the DS population.