Department of Forensic Medicine, CHU Montpellier, University of Montpellier, Montpellier, France.
IRMB, INM, University of Montpellier, INSERM, CHU Montpellier, (LBPC-PPC), Montpellier, France.
Int J Legal Med. 2021 Sep;135(5):2081-2089. doi: 10.1007/s00414-021-02558-3. Epub 2021 Mar 19.
Tau proteins are recognized biomarkers of neurodegeneration and neuronal damage in the cerebrospinal fluid (CSF). It has also been suggested that these CSF proteins could increase post-mortem due to neuronal death. The aim of this study was to investigate the changes in CSF total and phosphorylated tau (p-tau) levels in the early post-mortem interval (PMI), to determine whether these proteins could be relevant biomarkers of time since death.
Tau and p-tau levels were measured by ELISA in lumbar and cisternal CSF samples from 82 corpses (46 men, 36 women, mean age: 72.4 ± 15.2 years) with a PMI < 12 h. Forty-eight of them were considered neurologically healthy at the time of death. Rectal and tympanic temperatures were also measured in 37 individuals, and two validated temperature-based methods of PMI estimation were applied (Henssge's nomogram and Baccino's method).
CSF tau and p-tau levels were significantly increased, with respective median values of 3315 pg/mL and 68.5 pg/mL in the whole cohort, while lower but still increased levels were observed in neurologically healthy patients. Sub-occipital punctures systematically provided higher tau and p-tau values (p < 0.0001). Despite a great inter-individual variability, the concentrations of both biomarkers were positively correlated with the early PMI, with the highest correlation for cisternal p-tau (r = 0.50, p < 0.0001 in the whole cohort; r = 0.58, p = 0.0003 in the neurologically healthy patients). Higher levels of CSF biomarkers were observed for PMI > 6 h versus PMI ≤ 6 h, the discriminatory power of the biomarkers being higher in the subgroup of neurologically healthy patients. Based on cut-off values obtained by ROC curve analysis, the CSF biomarkers could rectify or adjust the time interval provided by the temperature-based methods in a significant number of cases. A predictive model combining tympanic temperature and cisternal tau values was found to be particularly accurate to assign individuals according to their PMI (≤ or > 6 h), with a Se of 83% and a Sp of 100% (AUC = 0.95).
Our findings suggest that CSF tau and p-tau proteins could serve as potential biomarkers of time since death, in association with tympanic temperature. The practical applicability of such an integrated approach has to be assessed by further studies.
tau 蛋白被认为是中枢神经系统（CSF）中神经退行性变和神经元损伤的生物标志物。也有人认为，这些 CSF 蛋白可能会因神经元死亡而在死后增加。本研究旨在探讨死后早期（PMI）CSF 总 tau（t-tau）和磷酸化 tau（p-tau）水平的变化，以确定这些蛋白是否可作为死亡时间的相关生物标志物。
对 82 例尸检（46 名男性，36 名女性，平均年龄：72.4±15.2 岁）死后 PMI<12 小时的腰椎和脑池 CSF 样本进行 ELISA 检测。其中 48 例在死亡时被认为是神经健康的。还测量了 37 个人的直肠和鼓室温度，并应用了两种经过验证的 PMI 估计的基于温度的方法（Henssge 列线图和 Baccino 方法）。
tau 和 p-tau 的 CSF 水平明显升高，整个队列的中位数分别为 3315pg/ml 和 68.5pg/ml，而神经健康患者的水平虽然较低，但仍有升高。枕下穿刺系统地提供了更高的 tau 和 p-tau 值（p<0.0001）。尽管个体间存在很大的变异性，但两种生物标志物的浓度与早期 PMI 呈正相关，脑池 p-tau 的相关性最高（整个队列中 r=0.50，p<0.0001；r=0.58，p=0.0003 在神经健康的患者中）。与 PMI≤6 小时相比，PMI>6 小时的 CSF 生物标志物水平更高，在神经健康患者的亚组中，生物标志物的判别能力更高。基于 ROC 曲线分析获得的截断值，CSF 生物标志物可以纠正或调整基于温度的方法提供的时间间隔，在大量病例中效果显著。发现结合鼓室温度和脑池 tau 值的预测模型对于根据 PMI（≤或>6 小时）分配个体特别准确，Se 为 83%，Sp 为 100%（AUC=0.95）。
我们的研究结果表明，CSF tau 和 p-tau 蛋白可能与鼓室温度一起作为死亡时间的潜在生物标志物。这种综合方法的实际适用性需要进一步研究来评估。
