Brain Sciences, Imperial College London, London, UK.
UK Dementia Research Institute Centre for Care Research and Technology, Imperial College London, London, UK.
J Neurol Neurosurg Psychiatry. 2024 Mar 13;95(4):356-359. doi: 10.1136/jnnp-2023-331854.
Traumatic 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.
Plasma 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.
Plasma 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.
Plasma 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.
创伤性脑损伤（TBI）与tau 病阿尔茨海默病和慢性创伤性脑病有关。先进的免疫分析显示，TBI 后早期血浆总 tau（t-tau）显著升高，但随后迅速正常化。丝氨酸 181 磷酸化的 tau（p-tau181）是一种经过充分验证的阿尔茨海默病标志物，可能潜在地引发进行性神经退行性变。我们测试了创伤后 p-tau181 浓度是否升高，并与进行性脑萎缩有关。
在 BIO-AX-TBI 队列中评估了中度至重度 TBI 后的血浆 p-tau181 和其他创伤后生物标志物，包括总 tau（t-tau）、神经丝轻链（NfL）、泛素羧基末端水解酶 L1（UCH-L1）和神经胶质纤维酸性蛋白（GFAP）（第一次样本平均 2.7 天，第二次样本在 10 天内，然后在 6 周、6 个月和 12 个月时进行，n=42）。在对齐的连续 MRI 中评估了脑萎缩率（n=40）。将浓度与阿尔茨海默病患者和无阿尔茨海默病患者以及健康对照组进行比较。
阿尔茨海默病患者的血浆 p-tau181 浓度明显升高，但 TBI 后并未升高，且在一年中保持稳定。TBI 后的 p-tau181 与灰质或白质的脑萎缩率无关。相比之下，大量与创伤相关的 t-tau、NfL、GFAP 和 UCH-L1 升高，NfL 和 t-tau 的浓度与脑萎缩率相关。
中度至重度 TBI 后第一年，血浆 p-tau181 未显著升高，水平与神经影像学测量的神经退行性变无关。
