Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Plasma proteomic biomarkers as mediators or moderators for the association between poor cardiovascular health and white matter microstructural integrity: The UK Biobank study.
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Beydoun May A, Beydoun Hind A, Noren Hooten Nicole, Li Zhiguang, Hu Yi-Han, Georgescu Michael F, Hossain Sharmin, Tanaka Toshiko, Bouhrara Mustapha, Maino Vieytes Christian A, Fanelli-Kuczmarski Marie T, Launer Lenore J, Evans Michele K, Zonderman Alan B
Аннотация
INTRODUCTION: The plasma proteome's mediating or moderating roles in the association between poor cardiovascular health (CVH) and brain white matter (WM) microstructural integrity are largely unknown.
METHODS: Data from 3953 UK Biobank participants were used (40-70 years, 2006-2010), with a neuroimaging visit between 2014 and 2021. Poor CVH was determined using Life's Essential 8 (LE8) and reversing standardized z-scores (LE8z _rev). The plasma proteome was examined as a potential mediator or moderator of LE8z _rev's effects on quantitative diffusion-weighted magnetic resonance imaging (dMRI) metrics.
RESULTS: LE8z_rev was significantly associated with deteriorated WM microstructural integrity, as reflected by lower tract-averaged fractional anisotropy (dMRI-FAmean), (β ± standared error (SE): -0.00152 ± 0.0003, p < 0.001) and higher tract-averaged orientation dispersion (dMRI-ODmean), (β ± SE:+0.00081 ± 0.00017, p < 0.001). Ten strongly mediating plasma proteins of 1463 were identified, with leptin as the principal driver.
DISCUSSION: Poor CVH is linked to poor WM microstructural integrity measures (lower FAmean and higher ODmean), mostly mediated through leptin.
HIGHLIGHTS: Up to 3953 UK Biobank participants were selected for this study. Poor cardiovascular health (CVH) was determined using Life's Essential 8. The plasma proteome was examined as a potential mediator or moderator of poor CVH's effect on dMRI metrics. Ten plasma proteins were identified with strong mediating effects, with leptin being the principal driver.
METHODS: Data from 3953 UK Biobank participants were used (40-70 years, 2006-2010), with a neuroimaging visit between 2014 and 2021. Poor CVH was determined using Life's Essential 8 (LE8) and reversing standardized z-scores (LE8z _rev). The plasma proteome was examined as a potential mediator or moderator of LE8z _rev's effects on quantitative diffusion-weighted magnetic resonance imaging (dMRI) metrics.
RESULTS: LE8z_rev was significantly associated with deteriorated WM microstructural integrity, as reflected by lower tract-averaged fractional anisotropy (dMRI-FAmean), (β ± standared error (SE): -0.00152 ± 0.0003, p < 0.001) and higher tract-averaged orientation dispersion (dMRI-ODmean), (β ± SE:+0.00081 ± 0.00017, p < 0.001). Ten strongly mediating plasma proteins of 1463 were identified, with leptin as the principal driver.
DISCUSSION: Poor CVH is linked to poor WM microstructural integrity measures (lower FAmean and higher ODmean), mostly mediated through leptin.
HIGHLIGHTS: Up to 3953 UK Biobank participants were selected for this study. Poor cardiovascular health (CVH) was determined using Life's Essential 8. The plasma proteome was examined as a potential mediator or moderator of poor CVH's effect on dMRI metrics. Ten plasma proteins were identified with strong mediating effects, with leptin being the principal driver.