Objective: To investigate whether plasma glial fibrillary acidic protein (GFAP) levels are related to glymphatic system function in Huntington’s disease (HD).

Background: Plasma GFAP levels has been shown correlated with the disease severities of manifested HD (mHD) patients. GFAP is involved in glymphatic system function. Glymphatic system could be reflected by analysis along the perivascular space (ALPS), free water (FW) scores and perivascular dilatation (PVS), and the later was dilated in HD with increased dilated PVS associated with worse HD severity.

Method: Tiantan Enroll HD program was established from September 2018 following standardized enroll HD procedure, ie., a series of clinical assessments were conducted, including UHDRS, TMS, SDMT, TFC, IS, and blood samples were taken at the time of enrollment. By October 2024, we have recruited over 140 participants carrying mutant HTT gene (mHTT). 67 mHTT subjects, including 50 mHD and 17 pre-manifest HD (PreHD), and 39 healthy controls (HC) were recruited in this study. PreHD is defined as participants with TMS of 5 or less. Diffusion MRI was used to calculate the ALPS index and FW scores, and the PVS proportion of basal ganglia (pPVS_BG) was calculated by EPC method using 3DT1 and 3DT2 sequences of all participants. The plasma GFAP levels were detected by ELISA.

Results: The plasma GFAP levels were significantly different among mHD, preHD and controls following general linear model analysis with age as a covariate (p=0.029). Post-hoc analysis showed a significant difference in plasma GFAP levels between mHD and HC (p=0.009); between mHD and PreHD (p=0.042); but not between PreHD and HC. The plasma GFAP levels were significantly correlated with TMS (p=0.002), SDMT (p=0.026), TFC (p=0.003) and IS (p=0.0003). In addition, the plasma GFAP levels were negatively correlated with mALPS (p=0.001), and significantly positively correlated with FW (p= 0.002) and pPVS_BG (p= 0.041) following correlation analysis and FDR correction. The associations between the plasma GFAP levels with mALPS index or FW scores remain after controlling enrollment age as a covariate.

Conclusion: In this study, we first demonstrated that the plasma GFAP levels in mHTT subjects were correlated with clinical manifestations and glymphatic system function.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/correlations-of-plasma-glial-fibrillary-acidic-protein-levels-with-glymphatic-system-impairment-in-huntingtons-disease/