Longitudinal changes in CSF alpha‐synuclein species reflect Parkinson's disease progression

Abstract

Our data show that CSF α-synuclein species have a dynamic pattern along the course of the disease, supporting their possible role as progression biomarkers for PD and their link with PD clinical phenotypes. © 2016 International Parkinson and Movement Disorder Society.

Differential effects of immunotherapy with antibodies targeting α-synuclein oligomers and fibrils in a transgenic model of synucleinopathy

“…The supernatant was collected, total protein concentration was measured, and all samples were adjusted to 0.1 mg/ml and stored at −80 °C. Total-, human total-, oligomeric- and phosphorylated at Ser129- (pS129) α-syn levels were measured using recently developed ELISA assays (Majbour et al, 2016a; Majbour et al, 2016b). Briefly, to capture total-, human total-or pS129-α-syn, a 384-well ELISA microplate was coated by overnight incubation at 4 °C with 0.1 μg/ml Syn-140 (sheep anti-α-syn polyclonal antibody) in 200 mM NaHCO 3 , pH 9.6 (50 μl/well), while 0.2 μg/ml of 5G4 (anti-aggregated α-syn mouse monoclonal antibody, EMD Millipore, MA, USA), was used to capture α-syn oligomers.…”

Systemic Activation of Nrf2 Pathway in Parkinson's Disease

“…Despite the limitations as the result of a relatively small sample size and the substantial homogeneous features (eg, early stages, mild–moderate presentation, strict selection criteria) of the population, Our findings suggest a potential interplay between the Nrf2 pathway and disease duration, indicating a compensatory attempt during the progression of the neurodegenerative process. Instead, the lowering of α‐syn oligomer levels found in patients with longer disease duration could theoretically reflect the fluctuations as a result of neuropathological modifications of PD during the disease course …”

α‐Synuclein Oligomers: A Study in Diversity

“…Since αSOs have been shown to induce toxicity via a variety of different mechanisms, they are important therapeutic targets; for example, by developing αSO specific antibodies or small molecules, which target the αSO, and thereby, block their toxic interactions. Furthermore, αSO specific antibodies would have clear potential in biomarker development; for example, by the detection of αSOs in CSF ,. However, in order to develop such an antibody, it is very important to identify the relevant αSO and cellular targets, if possible, using αSOs extracted from patients with PD.…”

“…Also, due to their smaller size, oligomers could more easily migrate to other cellular compartments . Because αSOs are soluble and directly involved in pathology, enabling their measurement, for example, in blood or cerebrospinal fluid (CSF),, could lead to new biomarkers for research, diagnosis, and clinical trials . Overall, the importance of αSOs in PD shares several parallels with amyloid‐beta oligomers that mediate several disease‐relevant toxic processes in AD …”