The abnormal
isoform of
prion protein (PrP) was detected by Western blotting and immunohistochemistry in all brains of 53 CJD and 20 GSS patients.
Formic acid pretreatment on
formalin fixed,
paraffin-embedded thin sections enhanced immunostaining of PrP in both congophilic and non-congophilic
kuru plaques which were absent in
sporadic CJD patients with short clinical courses. Newly developed pretreatment on tissue sections, called hydrolytic autoclaving, could detect fine granular deposits of PrP in the synaptic structures. The fine PrP grains were detected in almost all CJD patients, regardless of the length of clinical courses, but never in control brains. This method can be applied to long preserved
paraffin blocks. We analysed the PrP gene and found following variations.
Proline-to-
leucine change at
codon 102 was found in 10 Japanese families with GSS and 7
sporadic CJD patients with
kuru plaques.
Alanine-to-
valine change at
codon 117 was found in a big Alsatian family with cerebral
neurologic signs and
dementia. In one Japanese family, 4 members died from typical CJD and showed
glutamate-to-
lysine change at
codon 200. A 168 bp insertion which codes for 56
amino acids corresponding to 7 extra uninterrupted repeats of
proline-
glycine rich octapeptide (PHGGGWGQ) was detected in the N terminal region of PrP gene. This new insertion was found in a Japanese woman who showed slowly progressive
dementia for 7 years but lacked particular pathological changes, except for a few
kuru-like plaques in the cerebellum.