Circulating levels of vascular endothelial growth factor in patients with Alzheimer’s disease: A case-control study

Silva, Thays Martins Vital da; Stein, Angélica Miki; Coelho, Flávia Gomes de Melo; Rueda, André Veloso Lima; Camarini, Rosana; Galduróz, Ruth Ferreira

doi:10.1016/j.bbr.2022.114126

Cited by 6 publications

(4 citation statements)

References 46 publications

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“…It is worth noting that four studies included both the VaD and AD groups and compared them. 11,12,27,28 The VEGF level in the VaD group was marginally higher than in the AD group and there was no significant difference in the AD group, indicating that VEGF could be a diagnos- 11,12,27,28,[30][31][32][33][34][35][36] with comparatively few studies on East Asian, 10,[37][38][39][40][41][42] North American, [18][19][20][21]43 and South American 44,45 populations. Therefore, we focused on these European populations in the hope of reaching meaningful conclusions.…”

Section: Discussionmentioning

confidence: 92%

“…Most research on VEGF focuses on European populations, 11 , 12 , 27 , 28 , 30 , 31 , 32 , 33 , 34 , 35 , 36 with comparatively few studies on East Asian, 10 , 37 , 38 , 39 , 40 , 41 , 42 North American, 18 , 19 , 20 , 21 , 43 and South American 44 , 45 populations. Therefore, we focused on these European populations in the hope of reaching meaningful conclusions.…”

Section: Discussionmentioning

confidence: 99%

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Vascular endothelial growth factor is an effective biomarker for vascular dementia, not for Alzheimer's disease: A meta‐analysis

Xu,

Li,

et al. 2024

Alz & Dem Diag Ass & Dis Mo

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INTRODUCTIONVascular pathology is known to contribute to dementia and vascular endothelial growth factor (VEGF) is a well‐established biomarker associated with vascular alterations. Nonetheless, research findings on VEGF in Alzheimer's disease (AD) and vascular dementia (VaD) are inconsistent across various studies.METHODSWe conducted a meta‐analysis to elucidate relationships between VEGF and AD/VaD.RESULTSTwenty‐four studies were included. Pooled data showed that both blood and cerebrospinal fluid (CSF) VEGF levels were higher in VaD patients, whereas no significant difference was found between AD patients and healthy controls. However, the correlation between blood VEGF and AD was found among studies with AD pathology verification. And blood VEGF levels were higher in AD patients than controls in “age difference < 5 years” subgroup and CSF samples for European cohorts.DISCUSSIONThis study highlights that VEGF is more effective for the diagnosis of VaD and vascular factors are also an important contributor in AD.Highlights Vascular endothelial growth factor (VEGF) levels were higher in the vascular dementia group, but not in the overall Alzheimer's disease (AD) group. Correlation between VEGF and AD was found among studies with clear AD pathological verification. Elevated VEGF in the cerebrospinal fluid might be a diagnostic marker for AD in European populations.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor is an effective biomarker for vascular dementia, not for Alzheimer's disease: A meta‐analysis

Xu,

Li,

et al. 2024

Alz & Dem Diag Ass & Dis Mo

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“…These genes play a role in brain injury [2], stroke [3,4], and the progression of neurodegenerative disease [5], particularly Alzheimer's disease (AD). Within AD, disruptions in vascularization and circulation of the brain have been shown to contribute to neurodegeneration and the development of neuropathology [6][7][8][9][10][11][12][13]. As a result, VEGFs have become exciting targets for research to better understand vascular contributions to AD.…”

Section: Introductionmentioning

confidence: 99%

Association of 10 VEGF Family Genes with Alzheimer’s Disease Endophenotypes at Single Cell Resolution

Wu,

Libby,

Dumitrescu

et al. 2024

Preprint

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Background: The role of the vascular endothelial growth factors (VEGFs) in the pathogenesis of Alzheimer's disease (AD) has been recently described, including notable changes along the VEGFB/FLT1 signaling pathway. However, cell-type specific alterations are yet to be characterized in depth. In this study, we utilized a large single-nucleus RNA sequencing dataset (N = 424) to investigate the effect of 10 VEGF gene expression (VEGFA, VEGFB, VEGFC, VEGFD, PGF, FLT1, FLT4, KDR, NRP1, and NRP2) on cognitive performance and AD pathology, as well as on the associated VEGF signaling pathways in 8 cell types from postmortem human brains. Methods: The single-nucleus transcriptomes, derived from Dorsolateral Prefrontal Cortex (DLFPC) tissues of 424 unique donors from the Religious Orders Study and Memory and Aging Project (ROS/MAP; AD Knowledge Portal syn2580853), were collected by the Rush Alzheimer's Disease Center and processed at Columbia University Medical Center. Mean age of death of the cohort was 89 years, among which 68% were females, and 52% were clinical AD cases. Negative binomial mixed models implemented in Nebula R package were used for differential expression analysis between autopsy confirmed AD dementia and normal cognition groups, and for association analysis with amyloid burden, tangle burden, and both cross-sectional and longitudinal global cognitive function. Intercellular VEGF-associated communication pattern among cell types was also profiled using CellChat. Results: Higher microglia expressed FLT1, endothelial FLT4, astrocyte VEGFD, and oligodendrocyte precursor cell (opc) NRP1 expression associated with greater beta-amyloid burden. Higher oligodendrocyte VEGFB expression associated with greater beta-amyloid burden and worse cognitive trajectories, whereas higher VEGFB expression in inhibitory neurons was associated with lower beta-amyloid burden. Higher astrocyte NRP1 was associated with lower tangle burden. Higher expression of microglia and endothelial FLT1 associated with worse cognitive trajectories and lower cognition scores at the last clinic visit before death. As for association with diagnosis, prefrontal cortical FLT1 expression was upregulated in clinical AD patients compared to cognitively normal controls in both endothelial and microglial cells. For VEGF-associated intercellular communication, VEGFA-mediated signals contributed the most to the communication in both AD and normal cognition groups. Interestingly, although FLT1 expression was significantly elevated in AD endothelial cells, these cells still showed comparable VEGFA-FLT1 communication strength to the cognitively normal controls. Conclusions: Consistent with our previously reported results from bulk omics data, prefrontal cortical expression of FLT1 and FLT4 were associated with cross-sectional global cognitive function, longitudinal cognitive trajectories, and AD neuropathology, and our study showed these associations appear to be driven by endothelial and microglial cells. In contrast, VEGFB expression seems to have opposing effects on amyloid burden depending on the cell types, suggesting its more dynamic role in AD pathology.

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“…The levels of circulating VEGF increase in response to hypoxia, inflammation, and immunopathological processes. A significant difference was found between VEGF levels in Alzheimer’s disease patients and healthy individuals [ 15 ]. A number of studies have shown the diagnostic and prognostic value of circulating VEGF in arterial hypertension [ 16 ], coronary artery disease [ 17 ], myocardial infarction [ 18 ], peripheral arterial disease, and heart failure [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of VEGF-A and Its Receptors in Patients in Different Phases of Hemorrhagic and Ischemic Strokes

Babkina

Yadgarov

Острова

et al. 2022

CIMB

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Vascular endothelial growth factors (VEGFs) are important regulators of angiogenesis, neuroprotection, and neurogenesis. Studies have indicated the association of VEGF dysregulation with the development of neurodegenerative and cerebrovascular diseases. We studied the changes in serum levels of VEGF-A, VEGFR-1, and VEGFR-2 in patients at various phases of ischemic and hemorrhagic strokes. Quantitative assessment of VEGF-A, VEGFR-1, and VEGFR-2 in serum of patients with hemorrhagic or ischemic stroke was performed by enzyme immunoassay in the hyper-acute (1–24 h from the onset), acute (up to 1–7 days), and early subacute (7 days to 3 months) phases of stroke, and then compared with the control group and each other. Results of our retrospective study demonstrated different levels of VEGF-A and its receptors at various phases of ischemic and hemorrhagic strokes. In ischemic stroke, increased VEGFR-2 level was found in the hyper-acute (p = 0.045) and acute phases (p = 0.024), while elevated VEGF-A and reduced VEGFR-1 levels were revealed in the early subacute phase (p = 0.048 and p = 0.012, respectively). In hemorrhagic stroke, no significant changes in levels of VEGF-A and its receptors were identified in the hyper-acute phase. In the acute and early subacute phases there was an increase in levels of VEGF-A (p < 0.001 and p = 0.006, respectively) and VEGFR-2 (p < 0.001 and p = 0.012, respectively). Serum levels of VEGF-A and its receptors in patients with hemorrhagic and ischemic stroke indicate different pathogenic pathways depending on the phase of the disease.

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Circulating levels of vascular endothelial growth factor in patients with Alzheimer’s disease: A case-control study

Cited by 6 publications

References 46 publications

Vascular endothelial growth factor is an effective biomarker for vascular dementia, not for Alzheimer's disease: A meta‐analysis

Vascular endothelial growth factor is an effective biomarker for vascular dementia, not for Alzheimer's disease: A meta‐analysis

Association of 10 VEGF Family Genes with Alzheimer’s Disease Endophenotypes at Single Cell Resolution

Serum Levels of VEGF-A and Its Receptors in Patients in Different Phases of Hemorrhagic and Ischemic Strokes

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