Neuropathology of classic myotonic dystrophy type 1 is characterized by both early initiation of primary age-related tauopathy of the hippocampus and unique 3-repeat tauopathy of the brainstem
Neuropathology of classic myotonic dystrophy type 1 is characterized by both early initiation of primary age-related tauopathy of the hippocampus and unique 3-repeat tauopathy of the brainstem
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DOI：
10.1093/jnen/nlac097
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发表时间：
2022-11-04
影响因子：
3.2
通讯作者：
Iwaki, Toru
中科院分区：
文献类型：
--
作者：
Hamasaki, Hideomi;Maeda, Norihisa;Iwaki, Toru
强直性肌营养不良1型（DM 1）是一种遗传性常染色体显性疾病，可诱导转录本（包括MAPT）剪接改变，导致CNS中tau蛋白异常沉积。我们的特点是tau亚型异常沉积在4例典型的DM 1患者的大脑中，通过免疫组织化学使用亚型特异性抗体。所有患者，包括老年前期患者，均显示边缘区3-重复和4-重复tau蛋白的大量神经元缠结（NFT）和大脑皮质的轻度受累。仅在1例老年病例中观察到β淀粉样蛋白沉积，而所有其他病例中的皮质tau蛋白病与原发性年龄相关性tau蛋白病（PART）一致。在壳核和苍白球中，仅观察到少量tau沉积。脑干中的Tau沉积经常显示出具有3重复Tau显性NFT的DM 1特异性模式。此外，在脑干中偶尔观察到形态上类似于簇状星形胶质细胞和星形胶质细胞斑块的tau阳性星形胶质细胞;然而，它们主要由3-重复tau组成。因此，经典的DM 1显示边缘系统区域中的PART-like病理学的早期发作作为DM 1的类早老综合征和脑干中的异常剪接事件，导致3-重复tau显性积累，神经元和星形胶质细胞参与。
Myotonic dystrophy type 1 (DM1) is an inherited autosomal-dominant condition that induces altered splicing of transcripts, including MAPT, leading to a distinctive abnormal deposition of tau protein in the CNS. We characterized the tau isoforms of abnormal depositions in the brains of 4 patients with classic DM1 by immunohistochemistry using isoform-specific antibodies. All patients, including those of presenile age, showed numerous neurofibrillary tangles (NFTs) of both 3-repeat and 4-repeat tau in the limbic area and mild involvement in the cerebral cortex. Amyloid-beta deposition was only seen in 1 senile case while cortical tauopathy in all other cases was consistent with primary age-related tauopathy (PART). In the putamen and globus pallidus, only a few tau deposits were observed. Tau deposits in the brainstem frequently showed a DM1-specific pattern with 3-repeat tau dominant NFTs. Additionally, tau-positive astrocytes morphologically similar to tufted astrocytes and astrocytic plaques were occasionally observed in the brainstem; however, they were predominantly composed of 3-repeat tau. Thus, the classic DM1 showed both early onset of PART-like pathology in the limbic areas as a progeroid syndrome of DM1 and an abnormal splicing event in the brainstem leading to 3-repeat tau dominant accumulation with both neuronal and astrocytic involvement.