Primary age-related tauopathy (PART) is characterized by aggregation of tau in the mesial temporal lobe in older individuals. High pathologic tau stage (Braak stage) or a high burden of hippocampal tau pathology has been associated with cognitive impairment in PART. However, the potential underlying mechanisms are not well understood. Cognitive impairment in many neurodegenerative diseases correlates with synaptic loss, raising the question of whether synaptic loss also occurs in PART. To address this, we investigated synaptic changes associated with tau Braak stage and high tau pathology burden in PART using synaptophysin and phospho-tau immunofluorescence. We compared 12 cases of definite PART with 6 controls and 6 Alzheimer disease cases. In this study, the hippocampal CA2 region showed loss of synaptophysin puncta and intensity in cases of PART with either a high stage (Braak IV) or a high burden of neuritic tau pathology. There was also loss of synaptophysin intensity in CA3 associated with a high stage or high burden of tau pathology. Loss of synaptophysin was present in Alzheimer disease, but the pattern appeared distinct. These novel findings suggest the presence of synaptic loss associated with either a high hippocampal tau burden or a Braak stage IV in PART.

中文翻译：

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原发性年龄相关 tau 病中与 tau 病理相关的海马突触改变

原发性年龄相关 tau 蛋白病 (PART) 的特点是老年人内侧颞叶中 tau 蛋白聚集。高病理性 tau 分期（Braak 分期）或海马 tau 病理负担高与 PART 认知障碍相关。然而，潜在的潜在机制尚不清楚。许多神经退行性疾病中的认知障碍与突触丧失相关，这就提出了突触丧失是否也发生在 PART 中的问题。为了解决这个问题，我们使用突触素和磷酸化 tau 免疫荧光研究了 PART 中与 tau Braak 阶段和高 tau 病理负担相关的突触变化。我们将 12 例明确的 PART 病例与 6 例对照者和 6 例阿尔茨海默病病例进行了比较。在这项研究中，在具有高阶段 (Braak IV) 或高神经炎 tau 病理负担的 PART 病例中，海马 CA2 区域显示出突触素点和强度的丧失。CA3 中突触素强度的丧失也与 tau 病理的高阶段或高负担相关。阿尔茨海默病中存在突触素的缺失，但模式似乎很明显。这些新发现表明突触丢失的存在与 PART 中海马 tau 蛋白高负荷或 Braak IV 期相关。