Year: 2024
Type: conference-abstract
Abstract: Background Progression and age of onset are inversely linked to abnormal CAG repeat length in Huntington9s disease (HD). However, the disparity in clinical outcomes among patients with equal repetitions suggests that additional variables affect HD. Tau protein, encoded by the microtubule-associated protein tau (MAPT) gene, exhibits an inversion polymorphism that results in H1 and H2 variants. Furthermore, H1 homozygosity raises the risk of dementia in Parkinson’s disease and other tauopathies. Although Tau is implicated in HD neurodegeneration, the function of MAPT is yet uncertain. Aims To look at how MAPT haplotypes correlate with cerebrospinal fluid (CSF) biomarkers and clinical indications in a cohort of HD mutation carriers. Methods MAPT haplotyping was conducted through PCR testing for the intronic 238 bp deletion linked to the H2 haplotype. CSF biomarker concentrations in 79 carriers of gene mutations were determined by single molecule analysis (SIMOA). Clinical scales and cognitive indicators were assessed by the composite Unified Huntington9s Disease Rating Scale (cUHDRS) and the Symbol Digit Modalities Test (SDMT). Results The H1/H1 haplotype was significantly associated with higher CSF NfL and Tau concentrations in clear dependence with age. When the haplotype9s effect on clinical scales and cognitive indicators was examined, individuals manifesting symptoms with the H1 MAPT haplotype performed worse than H2 carriers (H2C). Conclusions Although further study is needed to explore the underlying molecular processes, the influence of the MAPT haplotype on HD clinical presentation indicates how aggravating H1 compared to the H2C9s protective effect.
Authors: Nil Salvat-Rovira, Anna Vázquez-Oliver, Elisa Rivas, Jesús Pérez-Pérez, Saül Martínez-Horta, Antonia Campolongo, Cristina Izquierdo, Rocío Pérez-González, Jaime Kulisevsky
Institution: Hospital de Sant Pau
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4402374577