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- W2896424526 abstract "Vascular endothelial growth factor (VEGF), the primary regulator of angiogenesis, is upregulated to enhance oxygen and glucose delivery to nutrient-deficient tissue. Amyloid disrupts VEGF signaling and may result in VEGF upregulation. This effect may explain why human studies in-vivo have found discrepant relationships between VEGF levels and Alzheimer's Disease (AD) diagnosis. We hypothesize that in individuals with high amyloid (Aβ+), higher CSF VEGF levels will partially compensate for Aβ effects on the brain, and therefore be associated with better aging outcomes: 1) a thicker cortex, 2) greater regional FDG-PET signal, and 3) better cognitive function. We evaluated 310 participants (92 cognitively intact, 149 mild cognitive impairment, 69 AD) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Separately in Aβ+ (CSF Aβ ≤ 192 pg/ml) and Aβ- participants, we used multiple linear regression (controlling for age, sex, education, APOE4 carrier status, CSF T-tau, and diagnosis) to relate CSF VEGF levels to: 1) MRI-derived cortical thickness in mean bilateral AD-relevant regions-of-interest (ROIs), grouping regions by their shared variances (Figure 1); 2) mean bilateral temporal lobe glucose metabolism (FDG-PET); and 3) established neuropsychological composite measures (executive function including language measures, and memory). False discovery rate (FDR) was applied to correct for multiple comparisons. We evaluated the direct and indirect effect of VEGF on executive function and memory through causal mediation analysis using the package mediation 4.4.6 in R (percentile bootstrap, B=1000). AD-relevant cortical thickness ROIs: A) Posterior cingulate, entorhinal cortex, temporal cortex (superior, middle, and inferior temporal gyri), B) parietal cortex (superior and inferior parietal gyri, precuneus). In Aβ+ participants only, higher CSF VEGF levels were significantly associated with a thicker temporal cortex (FDR-adjusted VEGF partial p=0.009, omnibus p<0.001), higher temporal lobe FDG-PET signal (VEGF partial p=0.007, omnibus p<0.001), and better executive function, driven largely by category naming (VEGF partial p=0.024, omnibus p<0.001). Mean bilateral temporal lobe FDG-PET signal mediated the relationship between CSF VEGF and executive function (estimated mediation effect=0.509; 95% CI [0.0693, 1.30]; p=0.004). Our results indicate that 1) CSF VEGF has regionally specific structural and metabolic associations in Aβ+ older adults, 2) CSF VEGF has an indirect effect on executive function, mediated by temporal lobe glucose metabolism, and 3) upregulation of VEGF in response to Aβ deposition may serve a compensatory neuroprotective role." @default.
- W2896424526 created "2018-10-26" @default.
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- W2896424526 date "2018-07-01" @default.
- W2896424526 modified "2023-10-16" @default.
- W2896424526 title "O2‐13‐02: RELATIONSHIP OF BRAIN STRUCTURE AND GLUCOSE METABOLISM TO VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF)" @default.
- W2896424526 doi "https://doi.org/10.1016/j.jalz.2018.06.2713" @default.
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