Coexistence of TDP-43 and tau pathology in neurodegeneration with brain iron accumulation type 1 (NBIA-1, formerly Hallervorden-Spatz syndrome)

Takashi Haraguchi, Seishi Terada, Hideki Ishizu, Osamu Yokota, Hidenori Yoshida, Naoya Takeda, Yuki Kishimoto, Naoko Katayama, Hiroshi Takata, Motohiro Akagi, Shigetoshi Kuroda, Yuetsu Ihara, Yosuke Uchitomi

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15 Citations (Scopus)


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 460g. 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.

Original languageEnglish
Pages (from-to)531-539
Number of pages9
Issue number5
Publication statusPublished - Oct 2011


  • Hallervorden-Spatz syndrome
  • Neurodegeneration with brain iron accumulation type 1
  • Neurofibrillary change
  • TDP-43 proteinopathy
  • Tauopathy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology


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