Evaluation of blood levels of Tau 181 protein in the Arabian horse: preliminary results

Extending the lifespan of a pet poses challenges related to brain aging, similar to those described in elderly people with Alzheimer's disease. In horses, a gradual increase in lifespan occurs. Some subjects, bred for affection or for sporting activity, are managed with care and are not used for food purposes. While indicators of brain aging such as amyloid beta and tau protein in the blood of dogs have long been demonstrated, the biochemical aspect in horses remains unexplored. Tau protein (pTau) is a highly soluble protein found in neurons. Under physiological conditions, it plays a crucial role in maintaining the proper functioning of neurons and the brain by promoting the formation and stabilization of cellular microtubules. However, during tauopathies or other neurodegenerative diseases such as Alzheimer's, abnormal hyperphosphorylation and subsequent aggregation of pTau occurs. Pathological pTau can be hyperphosphorylated at multiple epitopes, including amino acid 181. Its altered and insoluble form is aggregated and deposited in neurofibrillary tangles formed by paired helical filaments, which are one of the main anatomopathological signs of Alzheimer's disease. The aim of this research was to investigate the presence of hyperphosphorylated pTau 181 in the serum of horses clinically healty and without any evidence of cognitive impairment. For this purpose, a cohort of 30 Arabian horses was selected based on breed and age (Ethical committee authorization n°: 24/2024). A blood sample (collected during routine clinic examination) was drawn from each subject to determine serum pTau 181 concentrations using a horse species-specific sandwich ELISA kit (Horse Phosphorylated Tau 181, MyBioSource, Inc. San Diego, USA). The tested subjects were distributed into three age groups: Young (1-5 years; N=8); Adult (6-15 years; N=16); and Elderly (16-28 years; N=6). The mean pTau 181 values (± SD) were as follows: Young group 34.01 ± 12.86 pg/ml, Adult group 34.39 ± 21.43 pg/ml, Elderly group 39.69 ± 12.14 pg /ml. The statistical analysis, carried out using the non-parametric Kruskall-Wallis test, did not show statistically significant differences, however the trend towards an increase in pTau 181 content with increasing age was evident. The results of this preliminary study are in line with existing literature in humans. Numerous studies have been conducted in human medicine to identify plasma biomarkers useful for the early diagnosis of neurodegenerative diseases. Among these, pTau phosphorylated in different residues has been studied and a strong correlation emerged between their plasma concentration and cognitive dysfunction (1). Another interesting working hypothesis involves testing in the equine species, using a species-specific kit, of two plasma markers of neurodegenerative diseases previously validated in dogs: β-amyloid40 and β-amyloid42. In dogs, the score obtained from the Behavioral Scorecard for Aging, known as “CADES”, was correlated with the concentrations of βamyloid40 and β-amyloid42. For both forms of β-amyloid, a negative correlation compatible with the intracerebral accumulation of the substance during neurodegenerative diseases was observed (2). Further studies are necessary to obtain scientific evidence to support the hypothesis of using pTau and the two forms of β-amyloid as biomarkers of neurodegenerative pathology and accelerate the possible use of therapies. [1] Karikari et al. Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility, NAT REV NEUROL,18: 400-418, 2022. [2] Panek et al. Plasma amyloid beta concentrations in aged and cognitively impaired pet dogs, MOL NEUROBIOL, 58(2): 483-489,