Selected CSF biomarkers indicate no evidence of early neuroinflammation in Huntington disease.

Objective: To investigate CSF biomarkers of neuroinflammation and neurodegeneration in Huntington disease (HD) gene-expansion carriers compared to controls and to investigate these biomarkers in association with clinical HD rating scales and disease burden score. Methods: We collected CSF from 32 premanifest and 48 manifest HD gene-expansion carriers and 24 gene-expansion negative at-risk controls. We examined biomarkers of neuroinflammation (matrix metalloproteinase 9, C-X-C motif chemokine 13, terminal complement complex, chitinase-3-like-protein 1 [CHI3L1], and osteopontin [OPN]) and neurodegeneration (microtubule-associated protein tau, neurofilament light polypeptide [NFL], and myelin basic protein [MBP]). The study was approved by the Ethics Committee of the Capital Region of Denmark (H2-2011-085) and written informed consent was obtained from each participant before enrollment. Results: NFL was the only biomarker that increased in premanifest stages and no evidence of early involvement of neuroinflammation in HD was found. However, we found that the biomarkers for neurodegeneration, MBP and tau, increased during the disease course in manifest HD gene-expansion carriers and were associated with an increase of the neuroinflammation biomarkers CHI3L1 and OPN. Tau was also increased in all gene-expansion carriers with psychiatric symptoms compared to gene-expansion carriers without psychiatric symptoms. Conclusions: Neuroinflammation, which seems not to be an early event in our cohort, may be secondary to neurodegeneration in late HD. NFL is a possible disease burden correlate in HD, reflecting neuronal loss even before motor symptom onset, and may be useful as a dynamic biomarker in intervention studies.