alpha-synuclein and Chorea

Topics: alpha-Synuclein; Amyloid beta-Peptides; Antigens, CD; Cerebral Cortex; Chorea; Female; Glial Fibrillary Acidic Protein; Humans; Middle Aged; Nervous System Diseases; Prions

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.

Topics: 14-3-3 Proteins; Adult; Aged; Aged, 80 and over; alpha-Synuclein; Chorea; Corpus Striatum; Creutzfeldt-Jakob Syndrome; Female; Humans; Male; Middle Aged; Myoclonus; Neural Pathways; Neurons; Parkinsonian Disorders; Prions; Substantia Nigra; Ubiquitin; Young Adult

We examined the clinical features of familial (n = 26) and sporadic (n = 52) Parkinson's disease (PD) in patients presenting over the age of 40 years. Familial PD cases were tested for alpha-synuclein or parkin mutations as appropriate. No mutations were found in any of the families investigated. We found no between-group differences in the age at onset of PD, the pattern or severity of parkinsonian features, the dose of antiparkinsonian medications or treatment related complications. Cases of familial and sporadic PD in our cohort of patients display similar clinical features. This may suggest similar etiologies for both familial and sporadic PD.

Topics: alpha-Synuclein; Antiparkinson Agents; Autonomic Nervous System Diseases; Cerebellar Ataxia; Chorea; Cohort Studies; Databases, Factual; Dementia; Disease Progression; Dystonia; Female; Humans; Ligases; Male; Middle Aged; Nerve Tissue Proteins; Paralysis; Parkinson Disease; Synucleins; Tremor; Ubiquitin-Protein Ligases