Novel prion protein conformation and glycotype in Creutzfeldt-Jakob disease.
OBJECTIVE
To describe a novel molecular and pathological phenotype of Creutzfeldt-Jakob disease. Patient A 69-year-old woman with behavioral and personality changes followed by rapidly evolving dementia.


RESULTS
Postmortem examination of the brain showed intracellular prion protein deposition and axonal swellings filled with amyloid fibrils. Biochemical analysis of the pathological prion protein disclosed a previously unrecognized PrP(Sc) tertiary structure lacking diglycosylated species. Genetic analysis revealed a wild-type prion protein gene. The prion agent responsible for this atypical phenotype was successfully passaged to bank voles.


CONCLUSIONS
To our knowledge, our results define a new human prion disorder characterized by intracellular accumulation of a novel type of pathological prion protein.
Zanusso
Gianluigi
G
Department of Neurologic, University of Verona, Verona, Italy.
Polo
Alberto
A
Farinazzo
Alessia
A
Nonno
Romolo
R
Cardone
Franco
F
Di Bari
Michele
M
Ferrari
Sergio
S
Principe
Serena
S
Gelati
Matteo
M
Fasoli
Elisa
E
Fiorini
Michele
M
Prelli
Frances
F
Frangione
Blas
B
Tridente
Giuseppe
G
Bentivoglio
Marina
M
Giorgi
Alessandra
A
Schininà
Maria Eugenia
ME
Maras
Bruno
B
Agrimi
Umberto
U
Rizzuto
Nicola
N
Pocchiari
Maurizio
M
Monaco
Salvatore
S
D000368:Aged; D000818:Animals; D003411:Arvicolinae; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism* / Q000635:transmission; D017809:Fatal Outcome; D005260:Female; D005838:Genotype; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting; D013058:Mass Spectrometry; D016253:Microscopy, Immunoelectron; D010641:Phenotype; D018622:PrP 27-30 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018620:PrPSc Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D018620:PrPSc Proteins; D018622:PrP 27-30 Protein