Differential incorporation of tau isoforms in Alzheimer's disease.
Differential incorporation of tau isoforms in Alzheimer's disease.
复制标题
DOI：
10.3233/jad-2008-14101
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Marisol Espinoza;R. de Silva;D. Dickson;P. Davies
中科院分区：
文献类型：
--
作者：
Marisol Espinoza;R. de Silva;D. Dickson;P. Davies
成人大脑中表达了 6 种不同的 tau 亚型，但有关这些亚型的细胞分布的信息很少。 Tau 蛋白内含物存在于多种疾病的神经元中，偶尔也存在于神经胶质细胞中。先前对大脑匀浆进行的研究表明，tau 亚型可能有差异地融入到内含物中。为了进一步阐明阿尔茨海默病 (AD) 和其他神经退行性疾病中 tau 异构体组成的复杂问题，我们使用单克隆抗体来区分包含外显子 10 编码的 tau 残基 (4R tau) 和缺乏外显子 10 残基的 tau (3R tau)，用于对从 AD 和其他神经退行性疾病中分离的 tau 进行单标记和双标记免疫组织化学以及生化分析。使用这些抗体对 34 例 AD 病例的海马体进行免疫组织化学分析，结果显示 3R 和 4R tau 亚型均处于缠结状态。虽然生化研究表明，两种亚型都存在于 AD 海马和皮质中的不溶性 tau 聚集体中，但并非所有缠结似乎都用 3R 和 4R tau 特异性单克隆抗体标记。对进行性核上性麻痹和皮克氏病的类似研究证实，这些疾病的特征是纤维状病变中掺入特定亚型，但这两种疾病的病变均不完全由 3R tau 或 4R tau 亚型组成。
There are 6 different isoforms of tau expressed in the adult human brain, and little information is available on the cellular distribution of the isoforms. Tau inclusions are found in neurons and occasionally glia in a variety of diseases. Previous studies conducted on brain homogenates suggested that tau isoforms might be differentially incorporated into inclusions. To further elucidate the complex issue of tau isoform composition in Alzheimer's disease (AD) and other neurodegenerative diseases, monoclonal antibodies that differentiate between tau containing residues encoded by exon 10 (4R tau) and tau lacking exon 10 residues (3R tau) were used in single and double labeling immunohistochemistry as well as biochemical analyses of tau isolated from AD and other neurodegenerative diseases. Immunohistochemical analysis of the hippocampus in 34 AD cases performed with these antibodies showed both 3R and 4R tau isoforms in tangles. While biochemical studies showed that both isoforms were present in insoluble tau aggregates in AD hippocampus and cortex, not all tangles appear to be labeled with the 3R and 4R tau specific monoclonal antibodies. Similar studies in progressive supranuclear palsy and Pick's disease confirmed that these diseases were characterized by incorporation of specific isoforms in fibrillar lesions, but lesions in neither disease were exclusively composed of 3R tau or 4R tau isoforms.