Traumatic brain injury (TBI) and Alzheimer’s disease (AD) have overlapping mechanisms but it remains unknown if pathophysiological characteristics and cognitive trajectories in AD patients are influenced by TBI history. Here, we studied AD patients (stage MCI or dementia) with TBI history (AD n=110), or without (AD, n=110) and compared baseline CSF concentrations of amyloid beta 1–42 (Aβ42), phosphorylated tau181 (pTau181), total tau, neurofilament light chain (NfL), synaptosomal associated protein-25kDa (SNAP25), neurogranin (Ng), neuronal pentraxin-2 (NPTX2) and glutamate receptor-4 (GluR4), as well as differences in cognitive trajectories using linear mixed models. Explorative, analyses were repeated within stratified TBI groups by TBI characteristics (timing, severity, number). We found no differences in baseline CSF biomarker concentrations nor in cognitive trajectories between AD and AD patients. TBI >5 years ago was associated with higher NPTX2 and a tendency for higher SNAP25 concentrations compared to TBI ≤ 5 years ago, suggesting that TBI may be associated with long-term synaptic dysfunction only when occurring before onset or in a pre-clinical disease stage of AD.

中文翻译：

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阿尔茨海默病和脑外伤史患者的脑脊液生物标志物和认知轨迹


创伤性脑损伤（TBI）和阿尔茨海默病（AD）具有重叠的机制，但 AD 患者的病理生理特征和认知轨迹是否受到 TBI 病史的影响仍不清楚。在这里，我们研究了有 TBI 病史 (AD n=110) 或无 TBI 病史 (AD, n=110) 的 AD 患者（MCI 期或痴呆期），并比较了淀粉样蛋白 β 1-42 (Aβ42)、磷酸化 tau181 (pTau181) 的基线 CSF 浓度)、总 tau、神经丝轻链 (NfL)、突触体相关蛋白 25kDa (SNAP25)、神经粒蛋白 (Ng)、神经元五聚蛋白 2 (NPTX2) 和谷氨酸受体 4 (GluR4)，以及使用认知轨迹的差异线性混合模型。根据 TBI 特征（时间、严重程度、数量）在分层 TBI 组中重复进行探索性分析。我们发现 AD 和 AD 患者之间的基线 CSF 生物标志物浓度和认知轨迹没有差异。与 ≤ 5 年前的 TBI 相比，> 5 年前的 TBI 与较高的 NPTX2 和较高的 SNAP25 浓度趋势相关，这表明只有在发病前或临床前疾病阶段发生时，TBI 可能与长期突触功能障碍相关公元。