Circulating pTau181 and Genomic Background in Dogs: A Pilot Study on Neurobiological Aging

Aging in dogs mirrors key biological aspects of human aging, including molecular processes associated with neurodegeneration, making the dog a valuable comparative model. This pilot study investigated the integration of circulating blood biomarkers and genomic architecture to explore interindividual variability associated with neurobiological aging in dogs. Forty-eight dogs (31 purebred Labrador Retrievers and 17 mixed-breed dogs; age range: 2-15 years) were analyzed for serum phosphorylated tau at threonine 181 (pTau181). Genome-wide SNP genotyping was performed to characterize population structure, estimate pedigree- and ROH-based genomic inbreeding, and conduct an exploratory genome-wide association study (GWAS). Circulating pTau181 produced a quantifiable signal, but a subset of values fell below the assay's lower limit of detection and were coded as zero for statistical analysis. Data showed a continuous distribution, with mean values ranging from 6.1 to 13.4 pg/mL across demographic groups. No significant associations were observed between pTau181 concentrations and age category, sex, or breed group. Genomic analyses revealed clear population stratification between Labrador Retrievers and mixed-breed dogs, with significantly higher genomic homozygosity in Labradors (FROH = 0.26 ± 0.05) compared with mixed breeds (FROH = 0.12 ± 0.14; p = 0.00025). No significant correlations were detected between circulating pTau181 levels and genomic inbreeding coefficients. Exploratory GWAS identified a suggestive association between pTau181 concentrations and a locus on chromosome 29 (top SNP p = 5.57 × 10^-7), encompassing genes involved in proteostasis, neurodevelopment, and cellular metabolism. Although these associations did not reach genome-wide significance, they point to a biologically coherent genomic region potentially contributing to interindividual variability in tau blood levels. Overall, these findings provide preliminary evidence supporting the feasibility of combining circulating pTau181 measurements with genome-wide analyses to investigate molecular and genetic aspects of neurobiological aging in dogs within a comparative research framework.