Targeted Metabolomic Analysis of the Eye Tissue of Triple Transgenic Alzheimer's Disease Mice at an Early Pathological Stage

Alzheimer's disease (AD) is a severe neurodegenerative disease in older people. Despite some consensus on pathogenesis of AD established by previous researches, further elucidation is still required for better understanding. This study analyzed the eye tissues of 2- and 6-month-old triple transgenic AD (3 x Tg-AD) male mice and age-sex-matched wild-type (WT) mice using a targeted metabolomics approach. Compared with WT mice, 20 and 44 differential metabolites were identified in 2- and 6-month-old AD mice, respectively. They were associated with purine metabolism, pantothenate and CoA biosynthesis, pyruvate metabolism, lysine degradation, glycolysis/gluconeogenesis, and pyrimidine metabolism pathways. Among them, 8 metabolites presented differences in both the two groups, and 5 of them showed constant trend of change. The results indicated that the eye tissues of 3 x Tg-AD mice underwent changes in the early stages of the disease, with changes in metabolites observed at 2 months of age and more pronounced at 6 months of age, which is consistent with our previous studies on hippocampal targeted metabolomics in 3 x Tg-AD mice. Therefore, a joint analysis of data from this study and previous hippocampal study was performed, and the differential metabolites and their associated mechanisms were similar in eye and hippocampal tissues, but with tissue specificity.

Automated summary

This study analyzed the eye tissues of 2- and 6-month-old triple transgenic AD (3 x Tg-AD) male mice and identified differential metabolites associated with various metabolic pathways. The results showed that the eye tissues of 3 x Tg-AD mice underwent changes in the early stages of the disease, and these changes were more pronounced at 6 months of age. The joint analysis with previous hippocampal study revealed similar differential metabolites and mechanisms, but with tissue specificity.