Background
Alterations in amine metabolism have been implicated in Alzheimer’s disease (AD), but the relationships between plasma and cerebrospinal fluid (CSF) amine levels remain insufficiently understood.
Aim
To investigate longitudinal changes in amines in plasma and CSF, as well as their cross-matrix correlations, in male and female TgF344-AD transgenic rats compared with wild-type (WT) controls.
Method
LC-MS-based targeted metabolomics was used to quantify 60 plasma amines and 55 CSF amines in male and female TgF344-AD and WT rats at 12, 25, 50 and 85 weeks of age. Generalized linear models, Pearson correlations, and Fisher’s r-to-z transformation were applied for statistical analysis.
Results
In plasma, age- and sex-associated differences were observed. At 25 weeks, three amines (4-hydroxy-proline, homocitrulline, and hydroxylysine) showed significantly increased levels in male TgF344-AD rats after multiple-testing...
Show moreBackground
Alterations in amine metabolism have been implicated in Alzheimer’s disease (AD), but the relationships between plasma and cerebrospinal fluid (CSF) amine levels remain insufficiently understood.
Aim
To investigate longitudinal changes in amines in plasma and CSF, as well as their cross-matrix correlations, in male and female TgF344-AD transgenic rats compared with wild-type (WT) controls.
Method
LC-MS-based targeted metabolomics was used to quantify 60 plasma amines and 55 CSF amines in male and female TgF344-AD and WT rats at 12, 25, 50 and 85 weeks of age. Generalized linear models, Pearson correlations, and Fisher’s r-to-z transformation were applied for statistical analysis.
Results
In plasma, age- and sex-associated differences were observed. At 25 weeks, three amines (4-hydroxy-proline, homocitrulline, and hydroxylysine) showed significantly increased levels in male TgF344-AD rats after multiple-testing correction. Additional trend-level changes were observed at 12, 50, and 85 weeks. In CSF, no amines passed the significance threshold after multiple-testing correction, although descriptive age- and sex-associated patterns were observed, with earlier changes in males and later-stage trends in females. CSF–plasma correlations tended to be stronger in TgF344-AD rats than in WT rats, with relatively strong correlations for alpha-aminobutyric acid, citrulline, N6,N6,N6-trimethyl-lysine, and putrescine.
Conclusions
Body fluid, age- and sex-dependent amine alterations in CSF and plasma of TgF344-AD rats compared to WT controls provide important insights into AD disease processes and may aid early diagnosis and therapeutic targeting.
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