| Autor: |
Yau, Wai‐Ying Wendy, Yang, Hyun‐Sik, Carlyle, Becky C., Trombetta, Bianca A., Zhang, Can, Schultz, Aaron P., Pruzin, Jeremy J., Fitzpatrick, Colleen D, Kirn, Dylan, Rabin, Jennifer S., Buckley, Rachel F., Hohman, Timothy J., Rentz, Dorene M., Tanzi, Rudolph E., Johnson, Keith A., Sperling, Reisa A., Arnold, Steven E., Chhatwal, Jasmeer P. |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 24, Vol. 19, p1-4, 4p |
| Abstrakt: |
Background: Vascular dysfunction is increasingly recognized as an important partner in the pathogenesis of Alzheimer's disease (AD). Alterations in vascular endothelial‐derived growth factor (VEGF) pathways have been implicated as potential mechanisms. However, the specific impact of VEGF proteins in preclinical AD and their relationships with other AD and vascular pathologies during this critical early period remain to be elucidated. Method: We examined 316 cognitively unimpaired at baseline older adults from the Harvard Aging Brain Study (Table 1). VEGF family proteins (VEGF‐A, VEGF‐C, VEGF‐D, PlGF, VEGFR‐1) were measured in baseline fasting plasma using MSD V‐PLEX Angiogenesis Panel. Using linear mixed effects models, we examined the interactive effects of baseline plasma VEGF proteins and amyloid PET burden (Pittsburgh Compound‐B) on longitudinal cognitive decline (Preclinical Alzheimer Cognitive Composite‐5). We further investigated if effects on cognition may be mediated by longitudinal inferior temporal tau PET burden (Flortaucipir; subset n = 186) or hippocampal atrophy (subset n = 206). Lastly, we examined the impact of adjusting for baseline cardiovascular risk score or white matter hyperintensity volume (WMH). Result: High plasma VEGF‐A (β = 0.06, t = 3.23, p = 0.001) and low PlGF (β = ‐0.08, t = ‐3.88, p<0.001) each interacted with elevated baseline amyloid burden to slow prospective cognitive decline (Figure 1A). Concordantly, high VEGF‐A (β = ‐0.12, t = ‐4.56, p<0.001) and low PlGF (β = 0.09, t = 3.63, p<0.001) were associated with reduced longitudinal tau accumulation in those with elevated amyloid (Figure 1B). Moderated mediation analyses revealed that, under elevated amyloid, reduced tau accumulation fully mediated the effects of high VEGF‐A and partially mediated the effects of low PlGF (30%) on slower cognitive decline (Figure 2). There were no significant associations with hippocampal atrophy. The interactive effects of VEGF‐A and PlGF on tau and cognition remained significant after adjusting for cardiovascular risk score or WMH (p<0.003). Conclusion: High plasma VEGF‐A and low PlGF were associated with slower prospective cognitive decline in preclinical AD, which was fully (VEGF‐A) and partially (PlGF) mediated by reduced tau accumulation. These effects were distinct from conventional vascular risk and injury measures, highlighting VEGF‐A and PlGF as potential molecular targets in preclinical AD to modify the vascular‐AD synergy in combination with anti‐amyloid and traditional vascular risk reduction therapies. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Supplemental Index |
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