title: Neuropathology of Beta-propeller protein associated neurodegeneration (BPAN): a new tauopathy.
abstract: BACKGROUND
  Beta-propeller protein associated neurodegeneration (BPAN) is associated with mutations in the WD repeat domain 45 (WDR45) gene on chromosome Xp11 resulting in reduced autophagic flux. This study describes the clinical and neuropathological features of a female 51 year old BPAN case. The clinical history includes learning disability and progressive gait abnormalities since childhood followed by progressive dystonic features in young adulthood. Brain imaging revealed generalised brain atrophy and bilateral mineralisation of the globus pallidus and substantia nigra.
  
  
  RESULTS
  The major pathological findings were observed in the substantia nigra with excess iron deposition, gliosis, axonal swellings and severe neuronal loss. Iron deposition was also observed in the globus pallidus. There was extensive hyperphosphorylated-tau deposition in the form of neurofibrillary tangles, pre-tangles and neuropil threads. Furthermore, histological studies and immunoblotting confirmed a mixed Alzheimer type 3-and 4-repeat tau pathology. Microtubule-associated protein 1A/1B-light chain 3 (LC3) immunoblotting of brain homogenates indicated autophagic activity and may support the role of WDR45 in autophagy.
  
  
  CONCLUSIONS
  The widespread Alzheimer-type tau pathology in this disease indicates that this should be considered as a tauopathy and adds further support to the proposal that impaired autophagy may have a role in tauopathies.
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Paudel
authors.affiliation: Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Wiethoff
authors.affiliation: Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Bandopadhyay
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, UCL, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Bhatia
authors.affiliation: Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: de Silva
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. h.houlden@ucl.ac.uk.
authors.forename: H
authors.initials: H
authors.lastname: Houlden
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.|Reta Lila Weston Institute for Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Holton
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; C578284:WDR45 protein, human; D016875:tau Proteins