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

Human transmissible spongiform encephalopathies (TSEs) or prion diseases ar e neurodegenerative disorders of infectious, inherited or sporadic origin a nd include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS), kuru and fatal familial insomnia (FFI). Clinicopathologic fe atures of FFI differ markedly from other human TSEs. Previous studies demon strated selective neuronal vulnerability of parvalbumin positive (PV+) GABA ergic inhibitory interneurons in sporadic CJD and experimental TSEs, In thi s report we show uniform severe loss of PVS 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+ neuron s surrounded by isolectin-B4 positive perineuronal nets were severely affec ted in TSEs, suggesting a factor residing in this type of extracellular mat rix around PV+ neurons as modulator for the selective neuronal vulnerabilit y.