title: Selective neuronal vulnerability in human prion diseases. Fatal familial insomnia differs from other types of prion diseases.
abstract: 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.
authors.affiliation: Institute of Neurology, University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Guentchev
authors.forename: J
authors.initials: J
authors.lastname: Wanschitz
authors.forename: T
authors.initials: T
authors.lastname: Voigtländer
authors.forename: H
authors.initials: H
authors.lastname: Flicker
authors.forename: H
authors.initials: H
authors.lastname: Budka
mesh_terms: D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D010320:Parvalbumins / Q000096:biosynthesis*; D017096:Prion Diseases / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007319:Sleep Initiation and Maintenance Disorders / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid