Brain research bulletin · 2025
Bile acid profile and white matter microstructural changes in early Alzheimer's disease.
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Mo Ye, Peng Yifeng, Alzheimer's disease Neuroimaging Initiative (ADNI)
Аннотация
BACKGROUND: Although recent disease-modifying treatments such as Lecanemab have shown promise in reducing amyloid burden and modestly slowing cognitive decline in early Alzheimer's disease (AD), effective long-term interventions remain limited. Emerging evidence links dysregulated gut-liver bile-acid (BA) metabolism to AD pathology. We examined whether peripheral BA signatures correspond to early white-matter microstructure changes in prodromal AD.
METHODS: Baseline data were drawn from the Alzheimer's Disease Neuroimaging Initiative. One-hundred-twenty-seven participants (46 cognitively normal controls, 81 amnestic mild cognitive impairment [MCI]; 55-90 y) contributed serum concentrations of 33 BAs plus three predefined BA ratios, cerebrospinal-fluid biomarkers, and diffusion-tensor MRI. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AxD) diffusivities were derived using tract-based spatial statistics and atlas-based regions of interest.
RESULTS: Higher FA was associated with greater taurochenodeoxycholic acid, L-aspartate and L-asparagine, and with lower apocholic and 12-ketolithocholic acids. Elevated AxD, MD and RD tracked with reduced dehydrolithocholic acid and the glycolithocholic acid to chenodeoxycholic acid (GLCA/CDCA) ratio, and with higher palmitic acid. Participants with high cholic acid to chenodeoxycholic acid (CA/CDCA) ratio exhibited greater AxD in the left hippocampal cingulum; high GLCA/CDCA related to diffusivity increases in the right hippocampal cingulum and uncinate fasciculus. The glycodeoxycholic acid to taurodeoxycholic acid (GDCA/TDCA) ratio showed the strongest pattern, producing widespread AxD, MD and RD elevations in the uncinate fasciculus and cerebral peduncles and reduced FA in the fornix (p ≤ 0.0068).
CONCLUSION: Specific peripheral BA profiles-especially the gut-derived GDCA/TDCA ratio-mirror limbic and motor white-matter degeneration in amnestic MCI, independent of demographic and genetic risk. These findings implicate disrupted hepatic-microbial BA metabolism as a modifiable contributor to prodromal AD and highlight BA-targeted gut interventions as potential disease-modifying strategies.
METHODS: Baseline data were drawn from the Alzheimer's Disease Neuroimaging Initiative. One-hundred-twenty-seven participants (46 cognitively normal controls, 81 amnestic mild cognitive impairment [MCI]; 55-90 y) contributed serum concentrations of 33 BAs plus three predefined BA ratios, cerebrospinal-fluid biomarkers, and diffusion-tensor MRI. Fractional anisotropy (FA), mean (MD), radial (RD) and axial (AxD) diffusivities were derived using tract-based spatial statistics and atlas-based regions of interest.
RESULTS: Higher FA was associated with greater taurochenodeoxycholic acid, L-aspartate and L-asparagine, and with lower apocholic and 12-ketolithocholic acids. Elevated AxD, MD and RD tracked with reduced dehydrolithocholic acid and the glycolithocholic acid to chenodeoxycholic acid (GLCA/CDCA) ratio, and with higher palmitic acid. Participants with high cholic acid to chenodeoxycholic acid (CA/CDCA) ratio exhibited greater AxD in the left hippocampal cingulum; high GLCA/CDCA related to diffusivity increases in the right hippocampal cingulum and uncinate fasciculus. The glycodeoxycholic acid to taurodeoxycholic acid (GDCA/TDCA) ratio showed the strongest pattern, producing widespread AxD, MD and RD elevations in the uncinate fasciculus and cerebral peduncles and reduced FA in the fornix (p ≤ 0.0068).
CONCLUSION: Specific peripheral BA profiles-especially the gut-derived GDCA/TDCA ratio-mirror limbic and motor white-matter degeneration in amnestic MCI, independent of demographic and genetic risk. These findings implicate disrupted hepatic-microbial BA metabolism as a modifiable contributor to prodromal AD and highlight BA-targeted gut interventions as potential disease-modifying strategies.