Previous studies have suggested a relationship between the number of CAG triplet repeats in the HTT gene and neurodegenerative diseases not related to Huntington's disease (HD). This study seeks to investigate whether the number of CAG repeats of HTT is associated with the risk of developing certain tauopathies and its influence as a modulator of the clinical and neuropathological phenotype. Additionally, it aims to evaluate the potential of polyglutamine staining as a neuropathological screening. We genotyped the HTT gene CAG repeat number and APOE-ℰ isoforms in a cohort of patients with neuropathological diagnoses of tauopathies (n=588), including 34 corticobasal degeneration (CBD), 98 progressive supranuclear palsy (PSP) and 456 Alzheimer's disease (AD). Furthermore, we genotyped a control group of 1070 patients, of whom 44 were neuropathologic controls. We identified significant differences in the number of patients with pathological HTT expansions in the CBD group (2.7%) and PSP group (3.2%) compared to control subjects (0.2%). A significant increase in the size of the HTT CAG repeats was found in the AD compared to the control group, influenced by the presence of the Apoliprotein E (APOE)-ℰ4 isoform. Post-mortem assessments uncovered tauopathy pathology with positive polyglutamine aggregates, with a slight predominance in the neostriatum for PSP and CBD cases and somewhat greater limbic involvement in the AD case. Our results indicated a link between HTT CAG repeat expansion with other non-HD pathology, suggesting they could share common neurodegenerative pathways. These findings support that genetic or histological screening for HTT repeat expansions should be considered in tauopathies.

中文翻译：

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神经病理学证实的 tau 蛋白病中亨廷顿蛋白 CAG 重复：新见解

先前的研究表明，HTT基因中 CAG 三联体重复的数量与与亨廷顿病 (HD) 无关的神经退行性疾病之间存在关系。本研究旨在探讨HTT的 CAG 重复次数是否与发生某些 tau 病的风险相关，及其作为临床和神经病理表型调节剂的影响。此外，它的目的是评估聚谷氨酰胺染色作为神经病理学筛查的潜力。我们对一组神经病理学诊断为 tau蛋白病的患者 ( n = 588) 进行了HTT基因 CAG 重复数和 APOE-ℰ 亚型的基因分型，其中包括 34 例皮质基底节变性 (CBD)、98 例进行性核上性麻痹 (PSP) 和 456 例阿尔茨海默病 (AD) ）。此外，我们对 1070 名患者的对照组进行了基因分型，其中 44 名是神经病理对照。我们发现，与对照组 (0.2%) 相比，CBD 组 (2.7%) 和 PSP 组 (3.2%) 中病理性HTT扩张的患者数量存在显着差异。与对照组相比，AD 组中HTT CAG 重复序列的大小显着增加，这受到载脂蛋白 E (APOE)-ℰ4 亚型存在的影响。尸检评估发现 tau 蛋白病病理学具有阳性聚谷氨酰胺聚集体，PSP 和 CBD 病例的新纹状体稍占优势，而 AD 病例的边缘系统受累程度稍高。我们的结果表明HTT CAG 重复扩增与其他非 HD 病理之间存在联系，表明它们可能具有共同的神经退行性途径。这些发现支持在 tau 蛋白病中应考虑对HTT重复扩增进行遗传或组织学筛查。