Selective neuronal vulnerability in human prion diseases. Fatal familial insomnia differs from other types of prion diseases

Am J Pathol. 1999 Nov;155(5):1453-7. doi: 10.1016/S0002-9440(10)65459-4.


Human transmissible spongiform encephalopathies (TSEs) or prion diseases are neurodegenerative disorders of infectious, inherited or sporadic origin and include Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), kuru and fatal familial insomnia (FFI). Clinicopathologic features of FFI differ markedly from other human TSEs. Previous studies demonstrated selective neuronal vulnerability of parvalbumin positive (PV+) GABAergic inhibitory interneurons in sporadic CJD and experimental TSEs. In this report we show uniform severe loss of PV+ neurons also in other TSEs such as GSS, kuru, new variant and familial CJD. In contrast, these neurons are mostly well preserved, or only moderately reduced, in FFI. Only PV+ neurons surrounded by isolectin-B4 positive perineuronal nets were severely affected in TSEs, suggesting a factor residing in this type of extracellular matrix around PV+ neurons as modulator for the selective neuronal vulnerability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / metabolism
  • Brain / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neurons / pathology
  • Parvalbumins / biosynthesis*
  • Prion Diseases* / classification
  • Prion Diseases* / genetics
  • Prion Diseases* / metabolism
  • Prion Diseases* / pathology
  • Sleep Initiation and Maintenance Disorders* / classification
  • Sleep Initiation and Maintenance Disorders* / genetics
  • Sleep Initiation and Maintenance Disorders* / metabolism
  • Sleep Initiation and Maintenance Disorders* / pathology
  • gamma-Aminobutyric Acid / metabolism


  • Parvalbumins
  • gamma-Aminobutyric Acid