Tau protein in cerebrospinal fluid: a novel biomarker of the time of death?

Background: 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.

Methods: 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).

Results: 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).

Conclusion: 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.