title: Parkinson's disease, cortical dysfunction, and alpha-synuclein.
abstract: The ability to understand how Parkinson's disease neurodegeneration leads to cortical dysfunction will be critical for developing therapeutic advances in Parkinson's disease dementia. The overall purpose of this project was to study the small-amplitude cortical myoclonus in Parkinson's disease as an in vivo model of focal cortical dysfunction secondary to Parkinson's disease neurodegeneration. The objectives were to test the hypothesis that cortical myoclonus in Parkinson's disease is linked to abnormal levels of α-synuclein in the primary motor cortex and to define its relationship to various biochemical, clinical, and pathological measures. The primary motor cortex was evaluated for 11 Parkinson's disease subjects with and 8 without electrophysiologically confirmed cortical myoclonus (the Parkinson's disease + myoclonus group and the Parkinson's disease group, respectively) who had premortem movement and cognitive testing. Similarly assessed 9 controls were used for comparison. Measurements for α-synuclein, Aβ-42 peptide, and other biochemical measures were made in the primary motor cortex. A 36% increase in α-synuclein was found in the motor cortex of Parkinson's disease + myoclonus cases when compared with Parkinson's disease without myoclonus. This occurred without significant differences in insoluble α-synuclein, phosphorylated to total α-synuclein ratio, or Aβ-42 peptide levels. Higher total motor cortex α-synuclein levels significantly correlated with the presence of cortical myoclonus but did not correlate with multiple clinical or pathological findings. These results suggest an association between elevated α-synuclein and the dysfunctional physiology arising from the motor cortex in Parkinson's disease + myoclonus cases. Alzheimer's disease pathology was not associated with cortical myoclonus in Parkinson's disease. Cortical myoclonus arising from the motor cortex is a model to study cortical dysfunction in Parkinson's disease.
authors.affiliation: Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USA. jcaviness@mayo.edu
authors.forename: John N
authors.initials: JN
authors.lastname: Caviness
authors.forename: Lih-Fen
authors.initials: LF
authors.lastname: Lue
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Hentz
authors.forename: Charles H
authors.initials: CH
authors.lastname: Adler
authors.forename: Lucia
authors.initials: L
authors.lastname: Sue
authors.forename: Ramin
authors.initials: R
authors.lastname: Sadeghi
authors.forename: Erika
authors.initials: E
authors.lastname: Driver-Dunckley
authors.forename: Virgilio G
authors.initials: VG
authors.lastname: Evidente
authors.forename: Marwan N
authors.initials: MN
authors.lastname: Sabbagh
authors.forename: Holly A
authors.initials: HA
authors.lastname: Shill
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Walker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002540:Cerebral Cortex / Q000503:physiopathology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D009207:Myoclonus / Q000150:complications* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D051844:alpha-Synuclein; C075222:amyloid beta-protein (1-42)