Sporadic Creutzfeldt-Jakob disease VM1: phenotypic and molecular characterization of a novel subtype of human prion disease

Table 4 Comparison of demographic, histopathologic and molecular features among sCJD MM1, MV1, VV1, and VM1

sCJD subtype	MM1^#	MV1^#	VV1^§	VM1
n	74*	22	7	6
Female (%)	38 (51.4)	8 (38.1)	1 (14.3)	1 (16.7)
Age at onset (years)	69.7 ± 10.2	68.8 ± 9.4	46.0 ± 10.8	74.7 ± 5.6
Disease duration (months)	3.4 ± 1.8	3.7 ± 1.8	18.0 ± 3.2	20.5 ± 6.1
Histopathologic features
Vacuoles size	Small	Small	Intermediate	Intermediate
Lesion profile	Of variable severity in cerebral cortex, striatum, thalamus and cerebellum; hippocampus and amygdala spared	Virtually indistinguishable from MM1	Cerebral cortex and striatum severely affected, cerebellum relatively spared	Cerebral cortex and striatum moderately to severely affected, moderate changes in cerebellum
PrP deposits	Synaptic	Synaptic	Faint synaptic	Focally patchy in the molecular layer of cerebellum; faint synaptic elsewhere
PrP^res characteristics
WB profile of unglycosylated PrP^res	21 kDa	21 kDa	Doublet at 21 and 20 kDa	Doublet at 21 and 20 kDa
PrP^res glycoform ratio	Diglycosylated > unglycosylated isoform	Diglycosylated > unglycosylated isoform	Unglycosylated > diglycosylated isoform	Unglycosylated > diglycosylated isoform
C-terminal 12–13 kDa PrP^res fragments**	±	±	++	++
PrP^res migration shift at pH 6.9 vs 8.0	Yes	Yes	Less pronounced than in MM1/MV1	Less pronounced than in MM1/MV1

Continuous variables are expressed as mean ± SD. ^#sCJD MM1, MV1, and VV1 were from the ISNB cohort (2002–2021). ^§Given the very low incidence of sCJD VV1 cases in the ISNB cohort (n = 2), we also considered the demographic features of five previously published cases [12]. *from a consecutive series between 2017 and 2019. **Relative intensity of C-terminal 12–13 kDa fragments compared to the unglycosylated PrP^res signal at western blot. Legend: WB, western blot

ISSN: 2051-5960