| First Author | Pandey RS | Year | 2024 |
| Journal | Alzheimers Dement | Volume | 20 |
| Issue | 6 | Pages | 3987-4001 |
| PubMed ID | 38676929 | Mgi Jnum | J:351572 |
| Mgi Id | MGI:7702334 | Doi | 10.1002/alz.13851 |
| Citation | Pandey RS, et al. (2024) Metabolomics profiling reveals distinct, sex-specific signatures in serum and brain metabolomes in mouse models of Alzheimer's disease. Alzheimers Dement 20(6):3987-4001 |
| abstractText | INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation. METHODS: We investigated differences in serum and brain metabolites between the early-onset 5XFAD and late-onset LOAD1 (APOE4.Trem2*R47H) mouse models of AD to C57BL/6J controls at 6 months of age. RESULTS: We identified sex differences for several classes of metabolites, such as glycerophospholipids, sphingolipids, and amino acids. Metabolic signatures were notably different between brain and serum in both mouse models. The 5XFAD mice exhibited stronger differences in brain metabolites, whereas LOAD1 mice showed more pronounced differences in serum. DISCUSSION: Several of our findings were consistent with results in humans, showing glycerophospholipids reduction in serum of apolipoprotein E (apoE) epsilon4 carriers and replicating the serum metabolic imprint of the APOE epsilon4 genotype. Our work thus represents a significant step toward translating metabolic dysregulation from model organisms to human AD. HIGHLIGHTS: This was a metabolomic assessment of two mouse models relevant to Alzheimer's disease. Mouse models exhibit broad sex-specific metabolic differences, similar to human study cohorts. The early-onset 5XFAD mouse model primarily alters brain metabolites while the late-onset LOAD1 model primarily changes serum metabolites. Apolipoprotein E (apoE) epsilon4 mice recapitulate glycerophospolipid signatures of human APOE epsilon4 carriers in both brain and serum. |
