Objective: To identify new biomarkers of disease stage in HD.

Background: Proteomic approaches for CSF studies in Huntington’s disease (HD) have so far yielded limited information, but with more advanced techniques we aimed to discover new proteins involved in the pathophysiology of HD.

Methods: The study was conducted in accordance with the declaration of Helsinki and was approved by the local research ethics committee in Uppsala, Sweden. All participants signed an informed consent. A standardized protocol for lumbar puncture was applied. A clinically well characterized HD cohort was enrolled. Relative protein levels were measured with liquid chromotography-mass spectrometry. The study enrolled manifest HD-patients (n=13) and premanifest HD gene expansion carriers (n=12). Repeated samples after 1-4 years were obtained (n=10), and age- and sex matched gene negative controls (n=45).

Results: Protein level differences clearly separated the three groups. Upregulated proteins were mainly pro-inflammatory with roles in both innate- and adaptive immunity. Other upregulated proteins were involved in tissue remodeling, and plasticity. Downregulated proteins were involved in synaptic regulation, cell adhesion, neurite growth, and axonal transport. Alterations in proteins regulating calcium homeostasis, and the renin-angiotensin system were also discovered.

Conclusions: The results highlight the continued value of untargeted CSF proteomics approaches to discover disease related mechanisms. We aim to validate markers from selected pathways of interest with targeted assays.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cerebrospinal-fluid-proteomics-reveals-alterations-of-the-renin-angiotensin-system-in-huntingtons-disease/