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BACKGROUND: The hypothesis that amyloid deposition is the leading cause of Alzheimer's disease (AD) is supported by findings in transgenic animal models and forms the basis of clinical trials of anti-amyloid agents. According to this theory, amyloid deposition causes severe damage to neurons many years before onset of dementia via a cascade of several downstream effects. This hypothesis has, however, not yet been directly tested in human beings because of the very limited possibility of diagnosing amyloid deposition in vivo, which until recently required either brain biopsy or PET imaging with an on-site cyclotron and radiochemistry laboratory. Moreover, a clinical diagnosis of AD requires that patients have dementia, at which stage any effective treatment aimed at reducing amyloid deposition will probably be too late. RECENT DEVELOPMENTS: The amyloid imaging tracers flutemetamol, florbetapir, and florbetaben labelled with (18)F have been developed for PET; they can be produced commercially at central cyclotron sites and subsequently delivered to clinical PET scanning facilities. These tracers are currently undergoing formal clinical trials to establish whether they can be used to accurately image fibrillary amyloid and to distinguish patients with AD from normal controls and those with other diseases that cause dementia. They might also be used as biomarkers to predict development of AD before onset of dementia and to assess the effect of anti-amyloid therapy. Negative amyloid scans indicate absence of AD with a high level of accuracy, but healthy elderly volunteers might have positive amyloid scans, so their predictive value in isolation is less clear. Close association of in-vivo amyloid imaging results with post-mortem histopathological findings was shown with florbetapir in a phase 3 study. WHERE NEXT?: Therapeutic studies of anti-amyloid agents that include amyloid tracers as biomarkers are expected to be useful for drug development and to clarify the relation between amyloid removal and clinical effects. Once the (18)F tracers become available for diagnostic use, large-scale longitudinal studies will be needed to clarify their prognostic and diagnostic power in relation to age, risk factors, and AD subtypes. Ultimately, these tracers will hopefully clarify the pathophysiological role of amyloid in AD and contribute to development of new treatments.

Original publication




Journal article


Lancet Neurol

Publication Date





667 - 670


Aged, Alzheimer Disease, Brain, Humans, Plaque, Amyloid, Radionuclide Imaging