Phosphorylated α-synuclein (PS-129), a protein implicated in the pathogenesis of Parkinson’s disease (PD), was identified by mass spectrometry in human cerebrospinal fluid (CSF). A highly sensitive and specific assay was established and used to measure PS-129, along withtotal α-synuclein, in the CSF of patients with PD, other parkinsonian disorders such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), and healthy individuals (a total of ~600 samples). PS-129 CSF concentrations correlated weakly with PD severity and, when combined with total α-synuclein CSF concentrations, contributed to distinguishing PD from MSA and PSP. Further rigorous validation in independent cohorts of patients, especially those where samples have been collected longitudinally, will determine whether PS-129 CSF concentrations will be useful for diagnosing PD and for monitoring PD severity and progression.

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Background: The integrity of frontal systems responsible for voluntary control and their interaction with subcortical regions involved in reflexive responses were studied in patients with Parkinson's disease (PD). Previous studies have shown that patients with PD have impaired executive function, including deficits in attention, motor planning and decision making. Methods: Executive function was measured through eye movements: reflexive (stimulus driven) prosaccades and voluntary (internally guided) antisaccades. Patients with advanced idiopathic PD, off and on their optimal levodopa therapy, were tested on a prosaccade and an antisaccade task and compared with matched controls. Results: Levodopa significantly increased response time for reflexive prosaccades and reduced error rate for voluntary antisaccades. Conclusions: Consistent with our proposed model, patients with PD in the medicated state are better able to plan and execute voluntary eye movements. These findings suggest levodopa improves function of the voluntary frontostriatal system, which is deficient in PD.

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The results suggest that altered nigrostriatal and nigrocortical connectivity characterizes rapid eye movement sleep behavior disorder before onset of obvious motor impairment. The functional changes are discussed in the context of degeneration in dopaminergic and cognition-related networks.

α-synuclein is thought to play a key role in Parkinson’s disease (PD) because it is the major protein in Lewy bodies, and because its gene mutations, duplication, and triplication are associated with early-onset PD. There are conflicting reports as to whether serum and plasma concentrations of α-synuclein and anti-α-synuclein antibodies differ between PD and control subjects. The objectives of this study were to compare the levels of α-synuclein and its antibodies between individuals with typical PD (n = 14), atypical Parkinson syndromes (n = 11), idiopathic rapid eye movement sleep behavior disorder (n = 10), and healthy controls (n = 9), to assess the strength of association between these serum proteins, and to determine group sizes needed for a high probability (80% power) of detecting statistical significance for 25% or 50% differences between typical PD and control subjects for these measurements. Analysis of log-transformed data found no statistically significant differences between groups for either α-synuclein or its antibodies. The concentrations of these proteins were weakly correlated (Spearman rho = 0.16). In subjects with typical PD and atypical Parkinson syndromes, anti-α-synuclein antibody levels above 1.5 µg/ml were detected only in subjects with no more than four years of clinical disease. Power analysis indicated that 236 and 73 samples per group would be required for an 80% probability that 25% and 50% differences, respectively, in mean α-synuclein levels between typical PD and control subjects would be statistically significant; for anti-α-synuclein antibodies, 283 and 87 samples per group would be required. Our findings are consistent with those previous studies which suggested that serum concentrations of α-synuclein and its antibodies are not significantly altered in PD.

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Forty central amygdala neurons labelled with 2% Neurobiotin were categorized according to their distinctive bioelectrical membrane properties and classified physiologically by their hyperpolarized resting membrane potential (-74 mV), short duration medium afterhyperpolarization (239.2 ms), and non-accommodating response as Type A neurons (63%; N = 25/40), or as Type B neurons (37%; N = 15/40) by their depolarized resting membrane potential (-66 mV), long slow-afterhyperpolarization (1.8 s), and accommodation response. Visualized within subnuclei of the central amygdala, Neurobiotin-labelled Type A neurons were medium-size cells [16.5 +/- 3 x 10.7 +/- 2 mu m; length x width] with smooth, spine-free ovoid, pyramiform, and fusiform perikarya. Aspinous primary dendrites gave rise to distal dendrites covered with numerous small pedunculated spines; density of spines ranged from sparse to abundant. Type B central amygdala neurons were larger cells [23.9 +/- 5 x 14.9 +/- 4 mu m] with smooth, aspinous ovoid, polygonal, and pyramiform somata. Dendrites were aspinous and covered with variably sized varicosities. Two distinct populations of neurons exist within the central amygdaloid complex: the medium-size, spine-laden Type A defined neuron with its non-accommodating electrophysiological response and the larger aspinous, varicosity-laden Type B defined neuron with its accommodating response. In contrast to their neighboring "cortical-like" amygdala neurons, central amygdala neurons possess a "striatal-like" cytoarchitecture and electrophysiology.