Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Speech & Hearing Sciences, University of Washington, Seattle, WA, USA.
Nat Commun. 2021 Jun 8;12(1):3452. doi: 10.1038/s41467-021-23687-8.
Progressive apraxia of speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive apraxia of speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive apraxia of speech and may have consequences for development of 4R-tau targeting treatment.
进行性言语失用症是一种影响口语交流的神经退行性综合征。对 32 例经尸检证实的进行性言语失用症患者进行了长达 10 年的随访，研究了其分子病理学、生物化学、遗传学和纵向影像学。皮质基底节变性和进行性核上性麻痹（4R-tau 病）是最常见的潜在病理学。可感知的不同言语特征，加上发病年龄，可预测特定的 4R-tau 病；语音亚型和较年轻的年龄预测皮质基底节变性，韵律亚型和较年长的年龄预测进行性核上性麻痹。语音和韵律亚型在皮质-纹状体-苍白球-黑质-路易体网络中表现出不同的关系。生化分析显示聚集的 4R-tau 没有明显差异，而 tau H1 单倍型频率（69%）低于 1000 多例经尸检证实的 4R-tau 病。皮质基底节变性患者的下降速度更快，皮质退化程度更大，疾病持续时间更短，而进行性核上性麻痹则相反。这些发现有助于定义进行性言语失用症的病理生物学，并可能对开发针对 4R-tau 的治疗方法产生影响。
