title: FDG-PET and amyloid-PET imaging: the diverging paths.
abstract: OBJECTIVE
  The availability of PET neuroimaging tools for the in-vivo assessment of metabolic dysfunction and amyloid burden in Alzheimer's disease has opened important methodological and practical issues in the diagnostic design and the conduct of new clinical trials. This review, addressing the different molecular information that the amyloid-PET and fluorodeoxyglucose-PET (FDG-PET) tools can provide, highlights their diverging paths in Alzheimer's disease and possible new perspectives in research and clinical applications.
  
  
  RESULTS
  Senile plaques and neurofibrillary tangles are prominent neuropathological hallmarks in Alzheimer's disease and are considered to be targets for therapeutic intervention and biomarkers for diagnostic in-vivo imaging agents. Alzheimer's disease is a slowly progressing disorder, in which pathophysiological abnormalities, detectable in vivo by PET biomarkers, precede clinical symptoms by many years to decades. The unitary view of Alzheimer's disease as a sequential pathological pathway, with beta-amyloid (Aβ) as the only initial and causal event (the 'amyloid cascade hypothesis'), is likely to be progressively replaced by a more complex picture, also on the basis of recent PET imaging findings showing that neuronal injury biomarkers and tau pathology can be independent of β-amyloid deposition.
  
  
  CONCLUSIONS
  The different molecular paths that PET in-vivo biomarkers can reveal in the timeframe of Alzheimer's disease progression reflect the events leading to deposition of Aβ and phosphorylated tau, neuronal injury and neurodegeneration, which can run in parallel instead of in a sequential manner. The amyloid and neuronal injury paths may diverge along the Alzheimer's disease cascade and bear separate relationships with Alzheimer's disease symptoms and clinical phenotypes. All these evidences are crucial for the diagnosis and the development of new drugs aimed at slowing or preventing dementia.
authors.affiliation: Vita-Salute San Raffaele University, Nuclear Medicine Unit San Raffaele Hospital, Division of Neuroscience San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Perani
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D019788:Fluorodeoxyglucose F18; D006801:Humans; D049268:Positron-Emission Tomography
chemical_list: D016229:Amyloid beta-Peptides; D019788:Fluorodeoxyglucose F18