title: Coexistence of TDP-43 and tau pathology in neurodegeneration with brain iron accumulation type 1 (NBIA-1, formerly Hallervorden-Spatz syndrome).
abstract: We report here an autopsy case of sporadic adult-onset Hallervorden-Spatz syndrome, also known as neurodegeneration with brain iron accumulation type 1 (NBIA1), without hereditary burden. A 49-year-old woman died after a 27-year disease course. At the age of 22, she suffered from akinesia, resting tremor, and rigidity. At the age of 28, she was admitted to our hospital because of worsening parkinsonism and dementia. Within several years, she developed akinetic mutism. At the age of 49, she died of bleeding from a tracheostomy. Autopsy revealed a severely atrophic brain weighing 460 g. Histologically, there were iron deposits in the globus pallidus and substantia nigra pars reticulata, and numerous axonal spheroids in the subthalamic nuclei. Neurofibrillary tangles were abundant in the hippocampus, cerebral neocortex, basal ganglia, and brain stem. Neuritic plaques and amyloid deposits were absent. Lewy bodies and Lewy neurites, which are immunolabeled by anti-α-synuclein, were absent. We also observed the presence of TDP-43-positive neuronal perinuclear cytoplasmic inclusions, with variable frequency in the dentate gyrus granular cells, frontal and temporal cortices, and basal ganglia. TDP-43-positive glial cytoplasmic inclusions were also found with variable frequency in the frontal and temporal lobes and basal ganglia. The present case was diagnosed with adult-onset NBIA-1 with typical histological findings in the basal ganglia and brainstem. However, in this case, tau and TDP-43 pathology was exceedingly more abundant than α-synuclein pathology. This case contributes to the increasing evidence for the heterogeneity of NBIA-1.
authors.affiliation: Department of Neurology, National Hospital Organization Minami-Okayama Medical Center, Department of Neuropsychiatry, Okayama, Japan. haraguchit@s-okayama.hosp.go.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Haraguchi
authors.forename: Seishi
authors.initials: S
authors.lastname: Terada
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishizu
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokota
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yoshida
authors.forename: Naoya
authors.initials: N
authors.lastname: Takeda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kishimoto
authors.forename: Naoko
authors.initials: N
authors.lastname: Katayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takata
authors.forename: Motohiro
authors.initials: M
authors.lastname: Akagi
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Ihara
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Uchitomi
mesh_terms: D001284:Atrophy; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000145:classification / Q000378:metabolism / Q000473:pathology; D006211:Pantothenate Kinase-Associated Neurodegeneration / Q000378:metabolism* / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000378:metabolism*; D016875:tau Proteins / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016875:tau Proteins; D007501:Iron; D017853:Phosphotransferases (Alcohol Group Acceptor); C023088:pantothenate kinase