title: Pathological features of preclinical or early clinical stages of corticobasal degeneration: a comparison with advanced cases.
abstract: OBJECTIVE
  The manner in which pathological lesions of corticobasal degeneration (CBD) progress remains poorly understood. Because the pathology of early disease stages may be fundamental for elucidating a border between clinical and preclinical states of CBD, the present study aimed to detect preclinical or early clinical CBD cases by examining a series of forensic autopsy cases.
  
  
  METHODS
  A series of 887 brains from medicolegal autopsies was examined. Immunohistochemistry for tau (AT8, 3, and 4-repeat-tau) and Gallyas-Braak was applied for diagnosis. Neuropathological diagnosis of CBD followed criteria updated in 2002 by a working group.
  
  
  RESULTS
  Three autopsy cases (0.34%) were identified that fulfilled CBD pathological criteria. Two cases were preclinical or very early clinical cases without brain atrophy; the other case had exhibited a 5-year history of advanced frontotemporal dementia. Significant microscopic differences between the subclinical and clinical cases included occurrence of neuronal loss with spongiosis and gliosis, as well as a difference in degree of tau pathology in the superficial layer of the neocortical areas and white matter. Anatomical hierarchy of tau pathology in the brain was not evident, but asymmetric neocortical tau pathology that might influence the clinical phenotype was found in preclinical and early clinical cases.
  
  
  CONCLUSIONS
  The results revealed the pathological features of subclinical and early clinical CBD cases. Comparison with clinical CBD cases showed that neuronal loss, cortical atrophy and volume reduction of white matter may be involved in the occurrence of clinical symptoms of CBD. Additionally, immunohistochemistry is essential for detecting preclinical CBD cases, regardless of case selection.
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Neurology, Toyama University Hospital, Toyama, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hata
authors.affiliation: Division of Neurology, Kurobe City Hospital, Toyama, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Legal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Koshi
authors.initials: K
authors.lastname: Kinoshita
mesh_terms: D000368:Aged; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: corticobasal degeneration; immunohistochemistry; pathology; tauopathy