Category: Huntington's Disease
Objective: Explore the associations between CSF levels of neurofilament light chain (Nfl), total TAU (tTAU) and phosphorylated TAU (pTAU), structural brain damage and cognitive performance in HD.
Background: In HD, the variability observed in cognitive impairment suggests that beyond mHTT aggregation, other neuropathological mechanisms may contribute to brain damage and to the progression of cognitive deterioration .
Method: 46 gene-mutation carriers [n=25 premanifest/n=21 early symptomatic (eHD)] were enrolled. Nfl , tTAU and pTAU levels were quantified in CSF using SIMOA assay. Motor and functional assessments were performed. Behavior was assessed using the PBA-s and the Starkstein apathy scale. Cognition was assessed using the UHDRS cogscore, the PD-CRS and a comprehensive neuropsychological assessment covering several cognitive domains. Grey-matter volume (GMV)/cortical thickness (Cth) analysis were performed. All results were calculated controlling the effect of age, gender, education and disease burden.
Results: The CSF levels of Nfl, tTAU and pTAU were higher in the eHD. Nfl and tTAU levels were associated with global cognition. Apathy severity was strongly associated with Nfl, tTAU and pTAU. Higher Nfl levels were associated with lower memory, attention/executive functions and processing speed. Higher tTAU and pTAU were associated with worse memory, language, social cognition, and visuoperception. TAU-related cortical reductions found in the left frontal and parieto-temporal regions and right frontal regions were associated with worse cued-facilitated delayed recall, visual discrimination, facial and facial emotion recognition, and pseudoword reading. TAU-related GMV reductions were also found in several mid-temporal, parieto-occipital, frontal regions and bilateral hippocampus, showing a stron association with the reported cognitive parameters. Nfl-related GMV reductions found in the left caudate, thalamus, inferior temporo-occipital and angular gyrus, precuneus and mid frontal gyrus contributed to memory, attention and measures of executive functions. No Nfl-related Cth was found.
Conclusion: In HD, Nfl and TAU levels are associated with overlapped but also with clearly dissimilar patterns of brain damage and related neuropsychological deficits. This data highlights the need to explore the role of TAU pathology and other proteinopathies in the clinical expression of HD.
To cite this abstract in AMA style:
S. Martinez-Horta, J. Perez-Perez, R. Perez-Gonzalez, A. Horta-Barba, F. Sampedro, E. Rivas-Asensio, T. Xucla, M. Guasch, A. Campolongo, C. Izquierdo-Barrionuevo, J. Pagonabarraga, J. Kulisevsky. TAU pathology contributes to specific patterns of structural brain damage and neuropsychological heterogeneity in Huntington’s disease [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/tau-pathology-contributes-to-specific-patterns-of-structural-brain-damage-and-neuropsychological-heterogeneity-in-huntingtons-disease/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2020
MDS Abstracts - https://www.mdsabstracts.org/abstract/tau-pathology-contributes-to-specific-patterns-of-structural-brain-damage-and-neuropsychological-heterogeneity-in-huntingtons-disease/