The nigrostriatal pathway in Creutzfeldt-Jakob disease.
Parkinsonism, chorea, and dystonia are well-known clinical manifestations of Creutzfeldt-Jakob disease (CJD), but lesions of the nigrostriatal pathway have never been thoroughly studied. We performed a detailed neuropathologic study of the nigrostriatal pathway in 15 sporadic CJD and 2 variant CJD cases that included clinical correlations and assessment of neuron subtype loss, distribution of prion protein, alpha-synuclein, ubiquitin, and 14-3-3 aggregation. We found evidence of nigrostriatal pathway damage in these CJD cases. Dopaminergic neurons and striatal outflow neurons were markedly affected in sporadic CJD, whereas cholinergic interneurons were spared. In cases of CJD with chorea or myoclonus, there was less presynaptic dopaminergic loss than in cases of CJD with parkinsonism. The 2 variant CJD cases with parkinsonism or chorea showed severe cholinergic interneuron loss in the caudate and putamen, a pattern that differed from that found in sporadic CJD. alpha-Synuclein, ubiquitin, and 14-3-3 aggregation coexisted with prion protein aggregation, thereby generating mixed pathological features. These findings suggest a possible pathophysiological overlap of abnormal protein aggregation in CJD and Parkinson disease.
Vital
Anne
A
Université Victor Segalen-Bordeaux 2, Centre National de la Recherche Scientifique, Bordeaux Institute of Neuroscience, Bordeaux University Hospital, Bordeaux, France. anne.vital@chu-bordeaux.fr
Fernagut
Pierre-Olivier
PO
Canron
Marie-Hélène
MH
Joux
Julien
J
Bezard
Erwan
E
Martin-Negrier
Marie-Laure
ML
Vital
Claude
C
Tison
François
F
D048948:14-3-3 Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002819:Chorea / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009207:Myoclonus / Q000150:complications / Q000378:metabolism / Q000473:pathology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D025801:Ubiquitin / Q000378:metabolism; D055815:Young Adult; D051844:alpha-Synuclein / Q000378:metabolism
D048948:14-3-3 Proteins; D011328:Prions; D025801:Ubiquitin; D051844:alpha-Synuclein