Primary Feline Tauopathy: Clinical, Morphological, Immunohistochemical, and Genetic Studies.
Primary Feline Tauopathy: Clinical, Morphological, Immunohistochemical, and Genetic Studies.
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DOI：
10.3390/ani13182985
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发表时间：
2023-09-21
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影响因子：
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Tau蛋白病是一组神经退行性疾病，其中一种名为tau的特定蛋白质在神经元和神经胶质细胞中积累并形成聚集体。在人类中，这些疾病可能仅由这种蛋白质引起（原发性），也可能与另一种蛋白质共同作用引起（继发性）。原发性tau蛋白病在人类中常见，但在动物中罕见。我们分析了16只不同年龄的猫的tau病理发展情况。一只母猫在六年期间出现进行性精神状态和步态异常。脑部影像学显示大脑进行性萎缩。由于预后不良，这只猫在十岁时被实施安乐死。对脑组织的评估显示顶叶皮质的神经元和小脑的浦肯野细胞大量丢失。免疫组织化学检测发现神经元中有异常的tau蛋白聚集体（称为前缠结），少突胶质细胞中有（称为卷曲小体）。基因检测未发现任何与该疾病相关的已知基因改变。所研究的其他15只猫均未出现类似的临床症状或脑部变化。这是首次报道的成年猫原发性tau蛋白病病例，该猫在四岁时出现首批神经症状。
Tau蛋白病是一组以神经元和神经胶质细胞中过度磷酸化的tau蛋白病理性聚集为特征的神经退行性疾病。原发性tau蛋白病在人类中并不罕见，但在其他物种中极为罕见。我们评估了16只年龄在1到21岁、具有不同临床背景的猫与tau病理相关的临床、神经病理和基因改变情况。有趣的是，一只10岁的母猫有六年进行性的精神状态和步态异常病史。影像学研究显示广泛的皮质萎缩。由于预后不良，这只猫在十岁时被实施安乐死。神经病理损伤的特征是顶叶皮质大量神经元丢失，伴有明显的海绵状变性以及相关的中度反应性神经胶质增生，在大脑皮质的其他区域则较轻，并且小脑的浦肯野细胞丢失。免疫组织化学方法显示为4R - tau蛋白病，神经元中有颗粒状前缠结，少突胶质细胞中有卷曲小体。用几种磷酸化位点抗体（4Rtau、tau5、AT8、PFH、tau - P Thr181、tau - P - Ser 262、tau - P Ser 422）可识别沉积物，并与活性tau激酶（p38 - P Thr180/Tyr182和SAPK/JNK - P Thr138/Thr185）的颗粒状表达增加有关。基因研究显示MAPT的编码区保存完好。在同时处理的其他15只猫中未发现与tau病理相关的类似改变。据我们所知，这是首次报道的成年猫原发性4R - tau蛋白病病例，该猫在年轻时就出现神经症状，伴有严重的大脑和浦肯野细胞变性。
Tauopathies are a group of neurodegenerative diseases where a specific protein called tau accumulates and forms aggregates in neurons and glial cells. In humans, these diseases can be caused by only this protein (primary) or in combination with another one (secondary). Primary tauopathies are common in humans but rare in animals. We analyzed the development of tau pathology in 16 cats of different ages. A female cat showed progressive mental status and gait abnormalities over a six-year period. Brain imaging revealed a progressive shrinkage of the brain (atrophy). Due to a poor prognosis, the cat was euthanized at the age of ten years. Evaluation of the brain tissue showed significant loss of neurons in the parietal cortex and Purkinje cells in the cerebellum. Immunohistochemistry identified abnormal tau protein aggregates in neurons (referred to as pre-tangles) and oligodendrocytes (referred to as coiled bodies). Genetic testing did not reveal any known genetic alteration associated with this disease. None of the other 15 cats studied showed similar clinical signs or brain changes. This is the first reported case of primary tauopathy in an adult cat that presented the first neurological signs when she was four years old. Tauopathies are a group of neurodegenerative diseases characterized by the pathological aggregation of hyperphosphorylated tau in neurons and glia. Primary tauopathies are not uncommon in humans but exceptional in other species. We evaluate the clinical, neuropathological, and genetic alterations related to tau pathology in 16 cats aged from 1 to 21 years with different clinical backgrounds. Interestingly, a 10-year-old female cat presented a six-year progressive history of mental status and gait abnormalities. The imaging study revealed generalized cortical atrophy. Due to the poor prognosis, the cat was euthanatized at the age of ten. Neuropathological lesions were characterized by massive neuronal loss with marked spongiosis and associated moderate reactive gliosis in the parietal cortex, being less severe in other areas of the cerebral cortex, and the loss of Purkinje cells of the cerebellum. Immunohistochemical methods revealed a 4R-tauopathy with granular pre-tangles in neurons and coiled bodies in oligodendrocytes. Deposits were recognized with several phospho-site antibodies (4Rtau, tau5, AT8, PFH, tau-P Thr181, tau-P-Ser 262, tau-P Ser 422) and associated with increased granular expression of active tau kinases (p38-P Thr180/Tyr182 and SAPK/JNK-P Thr138/Thr185). The genetic study revealed well-preserved coding regions of MAPT. No similar alterations related to tau pathology were found in the other 15 cats processed in parallel. To our knowledge, this is the first case reporting a primary 4R-tauopathy with severe cerebral and Purkinje cell degeneration in an adult cat with neurological signs starting at a young age.
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影响因子：
4.2
作者：
Malbon, Alexandra J.;Sordo, Lorena;Hahn, Caroline
通讯作者：
Hahn, Caroline
DOI：
10.1007/s00018-022-04572-z
发表时间：
2022-10-21
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
通讯作者：
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DOI：
10.1016/j.cvsm.2012.04.003
发表时间：
2012-07-01
影响因子：
1.9
作者：
Landsberg, Gary M.;Nichol, Jeff;Araujo, Joseph A.
通讯作者：
Araujo, Joseph A.
影响因子：
5.6
作者：
通讯作者：
--
影响因子：
2.5
作者：
Fiock, Kimberly L.;Smith, Jodi D.;Hefti, Marco M.
通讯作者：
Hefti, Marco M.