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.