A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech.
A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech.
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DOI：
10.1038/s41467-021-23687-8
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发表时间：
2021-06-08
影响因子：
16.6
通讯作者：
Whitwell JL
中科院分区：
文献类型：
--
作者：
Josephs KA;Duffy JR;Clark HM;Utianski RL;Strand EA;Machulda MM;Botha H;Martin PR;Pham NTT;Stierwalt J;Ali F;Buciuc M;Baker M;Fernandez De Castro CH;Spychalla AJ;Schwarz CG;Reid RI;Senjem ML;Jack CR Jr;Lowe VJ;Bigio EH;Reichard RR;Polley EJ;Ertekin-Taner N;Rademakers R;DeTure MA;Ross OA;Dickson DW;Whitwell JL
进行性言语失用症是一种影响言语交流的神经退行性综合征。对32例尸检证实的进行性言语失用症患者进行了分子病理学、生物化学、遗传学和纵向影像学研究，这些患者随访超过10年。皮质基底节变性和进行性核上性麻痹（4 R-tau蛋白病）是最常见的基础病理。感知不同的语音特征，结合发病年龄，预测特定的4 R-tau蛋白病;语音亚型和年轻的年龄预测皮质基底节变性，韵律亚型和老年预测进行性核上性麻痹。语音和韵律亚型表现出不同的皮质-纹状体-苍白球-黑质-路易体网络内的关系。生化分析显示，聚集的4 R-tau没有明显差异，而tau H1单倍型频率（69%）低于1000+尸检证实的4 R-tau病变。皮质基底节变性患者比进行性核上性麻痹患者有更快的下降速度、更大的皮质变性和更短的病程。这些发现有助于定义进行性言语失用症的病理学，并可能对4 R-tau靶向治疗的发展产生影响。进行性言语失用症（PAOS）是一种影响言语交流的神经退行性综合征。在这里，作者对32例尸检证实的PAOS患者进行了10年以上的随访，并对其分子病理学、生物化学、遗传学和纵向神经影像学进行了表征。
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. Progressive apraxia of speech (PAOS) is a neurodegenerative syndrome of multiple etiologies which affects spoken communication. Here, the authors characterized the molecular pathology, biochemistry, genetics and longitudinal neuroimaging of 32 autopsy-confirmed patients with PAOS who were followed over 10 years.
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DOI：
10.1007/s12031-011-9589-0
发表时间：
2011-11
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Dickson DW;Kouri N;Murray ME;Josephs KA
通讯作者：
Josephs KA
影响因子：
12.7
作者：
Ahmed, Zeshan;Bigio, Eileen H.;Kovacs, Gabor G.
通讯作者：
Kovacs, Gabor G.
影响因子：
3.5
作者：
Baker, M;Litvan, I;Hutton, M
通讯作者：
Hutton, M
影响因子：
11.2
作者：
Arai, T;Ikeda, K;Mochizuki, A
通讯作者：
Mochizuki, A
影响因子：
14.5
作者：
DERENZI, E;VIGNOLO, LA
通讯作者：
VIGNOLO, LA