Alzheimer's disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI
Alzheimer's disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI
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中度至重度 TBI 后第一年，阿尔茨海默病标志物磷酸化 tau181 并未升高
DOI：
10.1136/jnnp-2023-331854
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Graham N
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文献类型：
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作者：
Graham N
研究背景创伤性脑损伤（traumatic brain injury，TBI）与tau蛋白病、阿尔茨海默病和慢性创伤性脑病有关.先进的免疫测定显示TBI后早期血浆总tau（t-tau）显著升高，但浓度随后迅速恢复正常。在丝氨酸-181（p-tau 181）处磷酸化的Tau是一种经过充分验证的阿尔茨海默病标志物，其可能潜在地导致进行性神经变性。我们测试了创伤后p-tau 181浓度是否升高并与进行性脑萎缩有关。方法血浆p-tau 181和其他创伤后生物标志物，包括总-tau（t-tau）、神经丝轻（NfL）、泛素羧基末端水解酶L1（UCH-L1）和胶质细胞酸性蛋白（GFAP），在BIO-AX-TBI队列中的中度至重度TBI后进行评估（第一次样本平均2.7天，第二次样本在10天内，然后6周，6个月和12个月，n=42）。在对齐的系列MRI中评估脑萎缩率（n=40）。浓度进行了比较，患者和没有阿尔茨海默氏病，与健康controls.ResultsPlasma p-tau 181浓度显着提高阿尔茨海默氏病患者，但不是TBI后，在那里的浓度是非升高，并保持稳定超过一年。TBI后P-tau 181不能预测灰质或白色脑萎缩率。相比之下，大量的创伤相关的t-tau，NfL，GFAP和UCH-L1的升高，与NfL和t-tau预测的脑萎缩rates.ConclusionsPlasma p-tau 181的浓度在中度至重度脑外伤后的第一年没有显着升高，水平不涉及神经退行性病变的神经影像学措施。
BackgroundTraumatic brain injury (TBI) is associated with the tauopathies Alzheimer’s disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer’s disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy.MethodsPlasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer’s disease, with healthy controls.ResultsPlasma p-tau181 concentrations were significantly raised in patients with Alzheimer’s disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates.ConclusionsPlasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.