Abstract
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.