title: Pantothenate kinase-associated neurodegeneration is not a synucleinopathy.
abstract: OBJECTIVE
  Mutations in the pantothenate kinase 2 gene (PANK2) are responsible for the most common type of neurodegeneration with brain iron accumulation (NBIA), known as pantothenate kinase-associated neurodegeneration (PKAN). Historically, NBIA is considered a synucleinopathy with numerous reports of NBIA cases with Lewy bodies and Lewy neurites and some cases reporting additional abnormal tau accumulation. However, clinicopathological correlations in genetically proven PKAN cases are rare. We describe the clinical, genetic and neuropathological features of three unrelated PKAN cases.
  
  
  METHODS
  All three cases were genetically screened for the PANK2 gene mutations using standard Sanger polymerase chain reaction sequencing. A detailed neuropathological assessment of the three cases was performed using histochemical and immunohistochemical preparations.
  
  
  RESULTS
  All cases had classical axonal swellings and Perls' positive iron deposition in the basal ganglia. In contrast to neuroaxonal dystrophies due to mutation of the phospholipase A2, group VI (PLA2G6) gene, in which Lewy body pathology is widespread, no α-synuclein accumulation was detected in any of our PKAN cases. In one case (20-year-old male) there was significant tau pathology comprising neurofibrillary tangles and neuropil threads, with very subtle tau pathology in another case.
  
  
  CONCLUSIONS
  These findings indicate that PKAN is not a synucleinopathy and, hence the cellular pathways implicated in this disease are unlikely to be relevant for the pathomechanism of Lewy body disorders.
authors.affiliation: Department of Molecular NeuroscienceQueen Square Brain Bank, UCL Institute of NeurologyRita Lila Weston Institute of Neurological Studies, London, UKDepartment of Pediatrics, University of Maryland, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Molecular NeuroscienceQueen Square Brain Bank, UCL Institute of NeurologyRita Lila Weston Institute of Neurological Studies, London, UKDepartment of Pediatrics, University of Maryland, Baltimore, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Paudel
authors.affiliation: Department of Molecular NeuroscienceQueen Square Brain Bank, UCL Institute of NeurologyRita Lila Weston Institute of Neurological Studies, London, UKDepartment of Pediatrics, University of Maryland, Baltimore, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Johnson
authors.affiliation: Department of Molecular NeuroscienceQueen Square Brain Bank, UCL Institute of NeurologyRita Lila Weston Institute of Neurological Studies, London, UKDepartment of Pediatrics, University of Maryland, Baltimore, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Courtney
authors.affiliation: Department of Molecular NeuroscienceQueen Square Brain Bank, UCL Institute of NeurologyRita Lila Weston Institute of Neurological Studies, London, UKDepartment of Pediatrics, University of Maryland, Baltimore, MD, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lees
authors.affiliation: Department of Molecular NeuroscienceQueen Square Brain Bank, UCL Institute of NeurologyRita Lila Weston Institute of Neurological Studies, London, UKDepartment of Pediatrics, University of Maryland, Baltimore, MD, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Holton
authors.affiliation: Department of Molecular NeuroscienceQueen Square Brain Bank, UCL Institute of NeurologyRita Lila Weston Institute of Neurological Studies, London, UKDepartment of Pediatrics, University of Maryland, Baltimore, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Department of Molecular NeuroscienceQueen Square Brain Bank, UCL Institute of NeurologyRita Lila Weston Institute of Neurological Studies, London, UKDepartment of Pediatrics, University of Maryland, Baltimore, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Revesz
authors.affiliation: Department of Molecular NeuroscienceQueen Square Brain Bank, UCL Institute of NeurologyRita Lila Weston Institute of Neurological Studies, London, UKDepartment of Pediatrics, University of Maryland, Baltimore, MD, USA.
authors.forename: H
authors.initials: H
authors.lastname: Houlden
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000378:metabolism* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000378:metabolism; D008297:Male; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D055815:Young Adult; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D016875:tau Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase