Objective: To evaluate whether cerebrospinal fluid (CSF) levels of alpha synuclein (Asyn), amyloid beta (Aβ) and tau change with disease progression and to evaluate whether lower CSF Asyn levels in PD correspond to lower levels of soluble Asyn in brain tissue.

Background: Parkinson disease (PD) is defined by the accumulation of aggregated Asyn in Lewy bodies and Lewy neurites. Widespread Aβ plaque accumulation occurs in a subset of PD patients, which is typically not accompanied by widespread tau accumulation. In our previous study we observed lower CSF Asyn and  Aβ_1-42 levels in PD compared to control participants, while CSF tau levels were similar between PD and control.

Method: CSF Asyn, Aβ_1-42 and tau were measured using commercial ELISAs. For postmortem brain tissue measurements, we utilized an in-house sandwich ELISA to measure Asyn levels in extracts of frozen postmortem brain tissue for 5 cortical regions, two limbic regions and 1 basal ganglia region.

Results: In this follow up study, we measured baseline CSF Asyn, Aβ_1-42 and tau in 190 PD and 48 control participants. Similar to the previous dataset, CSF Asyn and Aβ_1-42 were significantly lower in PD compared with controls, and CSF tau was not significantly different between PD and control. CSF Asyn positively correlated with tau in PD participants and controls, but Asyn only correlated with Aβ_1-42 in PD participants but not in controls. We also measured CSF Asyn, Aβ_1-42 and tau in 74 PD and 23 control participants who had a second lumbar puncture (LP2) between 2 and 9 years after the baseline LP (LP1). CSF Asyn remained lower in PD compared with controls in these longitudinal samples. However there was no significant change between LP1 and LP2 for Asyn. Mean levels of soluble Asyn in 8 brain regions were similar between 6 control and 39 PD cases, and Asyn levels did not correlate with either age or disease duration.

Conclusion: These results indicate that CSF Asyn levels are lower in PD compared to control and do not change in relation to disease duration. They also indicate that lower CSF levels in PD do not directly reflect levels of soluble Asyn in brain tissue, but instead may reflect altered transport or turnover in CSF.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-csf-measurements-of-alpha-synuclein-amyloid-beta-and-tau-in-parkinson-disease/