HTT gene intermediate alleles in neurodegeneration: evidence for association with Alzheimer's disease

Manuel Menéndez-González, Jordi Clarimón, Irene Rosas-Allende, Marta Blázquez, Esther Suárez San Martín, Ciara García-Fernández, Alberto Lleó, Oriol Dols-Icardo, Ignacio Illán-Gala, Germán Morís, Renée Ribacoba, Victoria Álvarez, Carmen Martínez

    Research output: Contribution to journalArticleResearch

    12 Citations (Scopus)


    © 2018 Elsevier Inc. Huntington's disease (HD) is an autosomal progressive neurodegenerative disorder caused by the expansion of CAG repeats in the HTT gene. Intermediate alleles (IAs) are in the range of 27–35 repeats and have been associated to a normal phenotype. The aim of this work was to analyze the association between intermediate huntingtin CAG-repeat alleles (IAs) and neurodegenerative diseases, other than HD. We screened the HTT CAG repeats in patients with Alzheimer's disease (AD) (n = 1126), Parkinson's disease (PD) (n = 610), and frontotemporal lobar degeneration (FTLD) (n = 225). We also studied 509 healthy controls (HCs). The relative frequency of IAs for each group was 6.03% in AD, 5.3% in FTLD, 3.5% in PD, and 2.9% in HCs. The frequency of IA was significantly higher among patients with AD when compared to HCs (p = 0.011, OR = 2.11, 95% CI = 1.19–3.74); no significant difference was observed in FTLD (p = 0.17; OR = 1.88, 95% CI = 0.85–4.03) and PD (p = 0.69; OR = 1.21; 95% CI (0.61–2.37) versus HCs. No atypical symptoms or clinical features distinctive of HD were found among carriers of IAs. We found 3 cases with CAG expansions within the pathological range, one diagnosed with AD, one with PD, and one with FTD. Results suggest that IAs might have a role in the pathogenesis of AD. In addition, HD patients might be misdiagnosed with other neurodegenerative diseases, particularly when CAG repeats are in the lower pathological range.
    Original languageEnglish
    Pages (from-to)215.e9-215.e14
    JournalNeurobiology of Aging
    Publication statusPublished - 1 Apr 2019


    • Cognitive decline
    • HTT gene
    • Huntington's disease
    • Intermediate alleles
    • Neurodegeneration


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