Extracellular deposition of Aβ peptides (or “plaques”) is one of the pathological hallmarks of Alzheimer’s disease (AD)i . The recent developments of molecular imaging tracers that bind to Aβ plaques in the brain have enabled in vivo detection of Aβ plaque deposition using PET. Non-invasive detection of Aβ deposition may potentially contribute to better diagnosis and management of patients with cognitive decline suspected of having neurodegenerative disorders. Additionally, confirmation of the presence of Aβ deposition among subjects and monitoring of changes in Aβ deposition may become critical in therapeutic interventions that are specifically designed to remove Aβ deposits from the brain. As of 2015, three compounds have been approved for imaging Aβ plaques by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA): 18F-florbetapir (Amyvid™, Eli Lilly); 18Fflutemetamol (Vizamyl™, GE Healthcare); and 18F-florbetaben (NeuraCeqTM, Piramal Pharma).
AD is the most common form of dementia. It is a neurodegenerative disease characterized by a constellation of clinical symptoms ranging from declines in short-term memory or executive function to behavioral changes, loss of language, alogia, impaired psychosocial function, and eventually death. The hallmarks of the disease have been classically defined by neuropathological changes including the formation of abundant Aβ plaques and neurofibrillary tangles of phosphorylated tau protein. Such protein aggregations are hypothesized to provoke or result from other pathologic processes observed in AD including inflammation, synaptic dysfunction, neuronal disconnection, and neuronal loss. However, the exact pathogenesis of AD and cascades of pathologic changes are still a matter of intense debate and investigation.
Recently the National Institute on Aging -Alzheimer’s Association (NIA-AA) and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), we well as the International Working Group published updated consensus guidelines for the neuropathological assessment of Alzheimer’s diseaseii,iii,iv . This guideline defines AD as a clinicopathological entity, instead of neuropathological disease confirmed at autopsy, with a set of clinical signs and symptoms of cognitive and behavioral changes that are typical for patients who have substantial AD neuropathological changes. The NIA-AA consensus guideline describes AD as a continuum of pathologic processes ranging from preclinical AD, and mild cognitive impairment (MCI), to dementia. This has set the stage for biomarkers, including imaging biomarkers to play a role in defining and diagnosing the various time-points (stages) along the AD continuum.