Metal accumulation as a potential modulator of tau phosphorylation in the common dolphin (Delphinus delphis): implications for marine environmental health

Cetaceans accumulate metals throughout their lifespan, serving as sentinels of marine environmental health. However, the chronic neurotoxicological risks of these contaminants remain understudied in wild populations. We evaluated two objectives in 14 stranded common dolphins ( Delphinus delphis ) from Spain (2025): (1) whether age and sex predict mercury (Hg), aluminum (Al), and cadmium (Cd) concentrations in the liver and brain; and (2) whether these concentrations are associated with tau-AT100 immunoreactivity, a marker of tau phosphorylation at pThr212/pSer214. AT100 immunoreactivity was quantified as the proportion of immunoreactive neuronal nuclei among all neuronal nuclei counted per section (112–170 per region) and was therefore modeled by Bayesian Beta-Binomial regression on the counts (logit link, PyMC v5), with tissue metal concentration and age class as predictors. A single primary hypothesis was designated a priori (hepatic Hg versus frontal cortex AT100); all remaining associations are reported as secondary or exploratory. Hepatic mercury showed a positive age gradient ( β = 0.49 , 95% highest density interval [HDI] = [0.06, 0.93]) and brain aluminum increased with age ( β = 0.69 , HDI = [0.24, 1.08]). For the primary association, a doubling of hepatic mercury corresponded to an increase of 8.2 percentage points in frontal cortex AT100 immunoreactivity (95% HDI = [4.3, 12.1]) after adjustment for age class; the estimate was insensitive to prior specification and to the exclusion of influential individuals. Hepatic aluminum showed associations of comparable magnitude, whereas brain aluminum did not exclude zero once age was included. Because age class covaries strongly with both metal burden and AT100 immunoreactivity in this cohort (Spearman ρ = 0.72 ), and because age entered the models as an ordinal class, these results identify associations rather than demonstrating an independent metal effect. They nonetheless support the integration of neuropathological markers into ecotoxicological risk assessment frameworks for long-lived marine apex predators.