Acta Neuropathologica

, Volume 112, Issue 5, pp 633–645

Amyotrophic lateral sclerosis with dementia: an autopsy case showing many Bunina bodies, tau-positive neuronal and astrocytic plaque-like pathologies, and pallido-nigral degeneration

  • Osamu Yokota
  • Kuniaki Tsuchiya
  • Tatsurou Oda
  • Takeshi Ishihara
  • Rohan de Silva
  • Andrew J. Lees
  • Tetsuaki Arai
  • Toshiki Uchihara
  • Hideki Ishizu
  • Shigetoshi Kuroda
  • Haruhiko Akiyama
Case Report


We report the case of a 54-year-old woman with mental retardation who developed frontotemporal dementia and amyotrophic lateral sclerosis (ALS) in the presenium. She presented with dementia at age 48, and motor neuron signs developed at age 53. She had no family history of dementia or ALS. Postmortem examination disclosed histopathological features of ALS, including pyramidal tract degeneration, mild loss of motor neurons, and many Bunina bodies immunoreactive for cystatin C, but not ubiquitin-positive inclusions. Unusual features of this case included severe neuronal loss in the substantia nigra and medial globus pallidus. The subthalamic nucleus, limbic system, and cerebral cortex were well preserved. In addition, neurofibrillary tangles (NFTs) were found in the frontal, temporal, insular, and cingulate cortices, nucleus basalis of Meynert, and locus coeruleus, and to a lesser degree, in the dentate nucleus, cerebellum, hippocampus, and amygdala. No ballooned neurons, tufted astrocytes, or astrocytic plaques were found. Tau immunostaining demonstrated many pretangles rather than NFTs and glial lesions resembling astrocytic plaques in the frontal and temporal cortices. This glial tau pathology predominantly developed in the middle to deep layers in the primary motor cortex, and was frequently associated with the walls of blood vessels. NFTs were immunolabeled with 3-repeat and 4-repeat specific antibodies against tau, respectively. Although the pathophysiological relationship between tau pathology and the selective involvement of motor neurons, substantia nigra, and globus pallidus was unclear, we considered that it might be more than coincidental.


Glial lesion Globus pallidus Vessel Neurofibrillary tangle Substantia nigra 


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Osamu Yokota
    • 1
    • 2
  • Kuniaki Tsuchiya
    • 1
    • 3
    • 4
  • Tatsurou Oda
    • 5
  • Takeshi Ishihara
    • 2
  • Rohan de Silva
    • 6
  • Andrew J. Lees
    • 6
  • Tetsuaki Arai
    • 1
  • Toshiki Uchihara
    • 7
  • Hideki Ishizu
    • 2
    • 8
  • Shigetoshi Kuroda
    • 2
  • Haruhiko Akiyama
    • 1
  1. 1.Department of NeuropathologyTokyo Institute of PsychiatryTokyoJapan
  2. 2.Department of NeuropsychiatryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  3. 3.Department of Laboratory Medicine and PathologyTokyo Metropolitan Matsuzawa HospitalTokyoJapan
  4. 4.Department of NeurologyTokyo Metropolitan Matsuzawa HospitalTokyoJapan
  5. 5.Department of Psychiatry, National Hospital OrganizationShimofusa Psychiatric CenterChibaJapan
  6. 6.Reta Lila Weston Institute of Neurological StudiesUniversity College LondonLondonUK
  7. 7.Department of NeuropathologyTokyo Metropolitan Institute for NeuroscienceTokyoJapan
  8. 8.Department of Laboratory MedicineZikei Institute of PsychiatryOkayamaJapan

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