title: A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism.
abstract: OBJECTIVE
  To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism.
  
  
  METHODS
  MEDLINE, ISI Web of Science, Cochrane Library, and Scopus electronic databases were searched for articles published until 29th March 2016 and included brain PET studies in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). Only articles published in English and in peer-reviewed journals were included in this review. Case-reports, reviews, and non-human studies were excluded.
  
  
  RESULTS
  Seventy-seven PET studies investigating the dopaminergic system, glucose metabolism, microglial activation, hyperphosphorilated tau, opioid receptors, the cholinergic system, and GABAAreceptors in PSP, MSA, and CBS patients were included in this review. Disease-specific patterns of reduced glucose metabolism have shown higher accuracy than dopaminergic imaging techniques to distinguish between parkinsonian syndromes. Microglial activation has been found in all forms of atypical parkinsonism and reflects the known distribution of neuropathologic changes in these disorders. Opioid receptors are decreased in the striatum of PSP and MSA patients. Subcortical cholinergic dysfunction was more severe in MSA and PSP than Parkinson's disease patients although no significant changes in cortical cholinergic receptors were seen in PSP with cognitive impairment. GABAAreceptors were decreased in metabolically affected cortical and subcortical regions in PSP patients.
  
  
  CONCLUSIONS
  PET molecular imaging has provided valuable insight for understanding the mechanisms underlying atypical parkinsonism. Changes at a molecular level occur early in the course of these neurodegenerative diseases and PET imaging provides the means to aid differential diagnosis, monitor disease progression, identify of novel targets for pharmacotherapy, and monitor response to new treatments.
authors.affiliation: Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK.
authors.forename: Flavia
authors.initials: F
authors.lastname: Niccolini
authors.affiliation: Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. marios.politis@kcl.ac.uk.
authors.forename: Marios
authors.initials: M
authors.lastname: Politis
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D035843:Biomedical Research / Q000639:trends; D019317:Evidence-Based Medicine; D006801:Humans; D057054:Molecular Imaging / Q000379:methods*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000175:diagnosis* / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D019275:Radiopharmaceuticals
keywords: Atypical parkinsonism; Corticobasal syndrome; Multiple system atrophy; Positron emission tomography; Progressive supranuclear palsy