Cognitive phenotype and neurodegeneration associated with Tau in Huntington's disease
Martinez-Horta, Saul (Institut de Recerca Sant Pau)
Pérez-Pérez, Jesús (Institut de Recerca Sant Pau)
Perez-Gonzalez, Rocío (Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL))
Sampedro, Frederic (Institut de Recerca Sant Pau)
Horta, Andrea (Institut de Recerca Sant Pau)
Campolongo, Antonia (Institut de Recerca Sant Pau)
Rivas-Asensio, Elisa (Institut de Recerca Sant Pau)
Puig-Davi, Arnau (Institut de Recerca Sant Pau)
Pagonabarraga Mora, Javier (Institut de Recerca Sant Pau)
Kulisevsky, Jaime (Institut de Recerca Sant Pau)
Universitat Autònoma de Barcelona

Data:	2024
Resum:	The clinical phenotype of Huntington's disease (HD) can be very heterogeneous between patients, even when they share equivalent CAG repeat length, age, or disease burden. This heterogeneity is especially evident in terms of the cognitive profile and related brain changes. To shed light on the mechanisms participating in this heterogeneity, the present study delves into the association between Tau pathology and more severe cognitive phenotypes and brain damage in HD. We used a comprehensive neuropsychological examination to characterize the cognitive phenotype of a sample of 30 participants with early-to-middle HD for which we also obtained 3 T structural magnetic resonance image (MRI) and cerebrospinal fluid (CSF). We quantified CSF levels of neurofilament light chain (NfL), total Tau (tTau), and phosphorylated Tau-231 (pTau-231). Thanks to the cognitive characterization carried out, we subsequently explored the relationship between different levels of biomarkers, the cognitive phenotype, and brain integrity. The results confirmed that more severe forms of cognitive deterioration in HD extend beyond executive dysfunction and affect processes with clear posterior-cortical dependence. This phenotype was in turn associated with higher CSF levels of tTau and pTau-231 and to a more pronounced pattern of posterior-cortical atrophy in specific brain regions closely linked to the cognitive processes affected by Tau. Our findings reinforce the association between Tau pathology, cognition, and neurodegeneration in HD, emphasizing the need to explore the role of Tau in the cognitive heterogeneity of the disease.
Ajuts:	Instituto de Salud Carlos III PI21/01758
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Annals of Clinical and Translational Neurology, Vol. 11 Núm. 5 (may 2024) , p. 1160-1171, ISSN 2328-9503

DOI: 10.1002/acn3.52031
PMID: 38544341

12 p, 1.5 MB

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