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- W2980563099 abstract "Studies suggest vascular endothelial growth factor A (VEGFA) is protective against Alzheimer's disease (AD). High levels of cerebrospinal fluid (CSF) VEGFA are associated with slower rates of hippocampal atrophy and less cognitive decline in AD biomarker-positive subjects, suggesting VEGFA is especially protective among those at highest risk for AD. APOE-ε4 carriers represent a highly susceptible population for AD and cognitive deficits. Thus, VEGF may confer distinct protection among APOE-ε4 carriers. Analysis of the entire VEGF family is necessary to determine which components within the VEGF signaling cascade contribute to neuroprotection. We evaluate interactions between prefrontal cortex expression of VEGF genes and APOE-ε4 genotype to clarify which VEGF ligands and receptors modify the association between ε4 and cognitive decline. Longitudinal cognitive data and autopsy measures of gene expression were obtained from the Religious Orders Study and Rush Memory and Aging Project. Binary logistic regression assessed APOE-ε4 x VEGF expression interactions on AD diagnosis. Linear and mixed-effects regression assessed APOE-ε4 x VEGF expression interactions on global cognition and cognitive change. Models covaried for age at death, cell type using cell-specific markers, and sex. Secondary analyses investigated VEGF associations stratified by APOE-ε4 status. Correction for multiple comparisons adjusted for all 10 genes in the VEGF family. NRP1 and NRP2 interacted with APOE-ε4 on AD diagnosis (corrected p-values≤0.05). NRP1 and VEGFA interacted with APOE-ε4 on cross-sectional cognitive performance (corrected p-values≤0.05). In all cases, higher expression of these genes was associated with worse outcomes among ε4 carriers, but better outcomes among ε4 non-carriers." @default.
- W2980563099 created "2019-10-25" @default.
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- W2980563099 date "2019-07-01" @default.
- W2980563099 modified "2023-10-16" @default.
- W2980563099 title "P3-138: APOE ε4 -SPECIFIC ASSOCIATIONS OF VEGF GENE FAMILY EXPRESSION WITH COGNITIVE AGING AND ALZHEIMER'S DISEASE" @default.
- W2980563099 doi "https://doi.org/10.1016/j.jalz.2019.06.3166" @default.
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