Association of serum vascular endothelial growth factor levels and cerebral microbleeds in patients with Alzheimer's disease

Zhang, J. B.; Li, M. F.; Zhang, H. X.; Li, Z. G.; Sun, Hairong; Wang, P. F.

doi:10.1111/ene.13030

Cited by 24 publications

(19 citation statements)

References 36 publications

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“…The seventh study demonstrated increased vascular endothelial growth factor levels in serum of AD patients with CMBs ( n = 47) vs. AD patients without CMBs ( n = 99) ( 48 ). The eighth study showed increased BBB dysfunction in the form of an increased CSF/serum albumin ratio in patients with cognitive decline with CMBs ( n = 15) compared with patients with cognitive decline but no CMBs ( n = 13) ( 50 ).…”

Section: Resultsmentioning

confidence: 99%

Blood-Brain Barrier Dysfunction in Small Vessel Disease Related Intracerebral Hemorrhage

et al. 2018

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Background and Purpose: Hypertensive vasculopathy and cerebral amyloid angiopathy are the two most common forms of cerebral small vessel disease. Both forms are associated with the development of primary intracerebral hemorrhage, but the pathophysiological mechanisms underlying spontaneous vessel rupture remain unknown. This work constitutes a systematic review on blood-brain barrier dysfunction in the etiology of spontaneous intracerebral hemorrhage due to cerebral small vessel disease.Methods: We searched Medline (1946–2018) and Embase (1974–2018) for animal and human studies reporting on blood-brain barrier dysfunction associated with intracerebral hemorrhage or cerebral microbleeds.Results: Of 26 eligible studies, 10 were animal studies and 16 were in humans. The authors found indications for blood-brain barrier dysfunction in all four animal studies addressing hypertensive vasculopathy-related intracerebral hemorrhage (n = 32 hypertensive animals included in all four studies combined), and in four of six studies on cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 47). Of the studies in humans, five of six studies in patients with cerebral amyloid angiopathy-related intracerebral hemorrhage (n = 117) and seven out of nine studies examining intracerebral hemorrhage with mixed or unspecified underlying etiology (n = 489) found indications for blood-brain barrier dysfunction. One post-mortem study in hypertensive vasculopathy-related intracerebral hemorrhage (n = 82) found no evidence for blood-brain barrier abnormalities.Conclusions: Signs of blood-brain barrier dysfunction were found in 20 out of 26 studies. Blood-brain barrier integrity deserves further investigation with a view to identification of potential treatment targets for spontaneous intracerebral hemorrhage.

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Section: Resultsmentioning

confidence: 99%

Blood-Brain Barrier Dysfunction in Small Vessel Disease Related Intracerebral Hemorrhage

et al. 2018

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“…This discrepancy may be due, in part, to the fact that there is mixed epidemiological evidence of risk and resilience when measuring VEGF. High levels of serum VEGF have been associated with an increased risk of stroke (Pikula et al, 2013) and more frequent cerebral microbleeds among individuals with Alzheimer's disease (Zhang et al, 2016), while CSF VEGF levels have been reported to be higher (Tarkowski et al, 2002), lower (Guo, Alexopoulos, & Perneczky, 2013), and equivalent (Blasko et al, 2006) among individuals with AD compared to controls. Perhaps VEGF-related genes like PROK1 will provide clues to help unravel the complex associations among VEGF, cerebrovascular disease, and AD.…”

Section: Discussionmentioning

confidence: 99%

Genetic resilience to amyloid related cognitive decline

Hohman

Dumitrescu

Cox

et al. 2016

Brain Imaging and Behavior

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Preclinical Alzheimer's disease (AD) is characterized by amyloid deposition in the absence of overt clinical impairment. There is substantial heterogeneity in the long-term clinical outcomes among amyloid-positive individuals, yet limited work has focused on identifying molecular factors driving resilience from amyloid-related cognitive impairment. We apply a recently developed predicted gene expression analysis (PrediXcan) to identify genes that modify the association between baseline amyloid deposition and longitudinal cognitive changes. Participants free of clinical AD (n=631) were selected from the AD Neuroimaging Initiative (ADNI) who had a baseline positron emission tomography measure of amyloid deposition (quantified as a standard uptake value ratio), longitudinal neuropsychological data, and genetic data. PrediXcan was used to impute gene expression levels across 15 heart and brain tissues. Mixed effect regression models assessed the interaction between predicted gene expression levels and amyloid deposition on longitudinal cognitive outcomes. The predicted gene expression levels for two genes in the coronary artery (CNTLN, PROK1) and two genes in the atrial appendage (PRSS50, PROK1) interacted with amyloid deposition on episodic memory performance. The predicted gene expression levels for two additional genes (TMC4 in the basal ganglia and HMBS in the aorta) interacted with amyloid deposition on executive function performance. Post-hoc analyses provide additional validation of the HMBS and PROK1 effects across two independent subsets of ADNI using two additional metrics of amyloid deposition. These results highlight a subset of unique candidate genes of resilience and provide evidence that cell-cycle regulation, angiogenesis, and heme biosynthesis likely play a role in AD progression.

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“…Interestingly, oncological studies have shown that VEGF may serve as a serum biomarker for angiogenic processes that are associated with the progression of different forms of cancer, such as colorectal tumors [ 24 ]. In AD, one study showed increased serum VEGF levels in AD patients of microbleeds whereas another study demonstrates [ 25 ] lower levels of serum VEGF in patients compared to age-matched controls [ 26 ], illustrating its suitability as a potential biomarker for AD.…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor remains unchanged in cerebrospinal fluid of patients with Alzheimer’s disease and vascular dementia

et al. 2018

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BackgroundIncreasing evidence suggests that cerebral vascular dysfunction is associated with the early stages of Alzheimer’s disease (AD). Vascular endothelial growth factor (VEGF) is one of the key players involved in the development and maintenance of the vasculature. Here, we hypothesized that VEGF levels in cerebrospinal fluid (CSF) may be altered in AD patients with vascular involvement, characterized by the presence of microbleeds (MB), and in vascular dementia (VaD) patients compared to controls.MethodsVEGF levels were determined by electrochemilumiscence Meso Scale Discovery (MULTI-SPOT Assay System) in CSF from age-matched groups of controls with subjective cognitive decline (n = 21), AD without MB (n = 25), AD with MB (n = 25), and VaD (n = 21) patients.ResultsThe average level of VEGF in the different groups was 2.8 ± 1 pg/ml CSF. Adjusted for age and gender, no significant differences were detected between groups (p > 0.5). However, we detected a significant correlation between the concentration of VEGF in the CSF and age (r = 0.22, p = 0.03). In addition, males (n = 54) revealed higher VEGF levels in their CSF compared to females (n = 38) (males = 3.08 ± 0.769 pg/ml (mean ± SD), females = 2.6 ± 0.59; p = 0.006), indicating a gender-related regulation.ConclusionOur study suggests that VEGF levels in the CSF do not reflect the cerebral vascular alterations in either AD or VaD patients. The observed associations of VEGF with age and gender may indicate that VEGF reflects normal aging and that males and females may differ in their aging process.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0385-8) contains supplementary material, which is available to authorized users.

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Association of serum vascular endothelial growth factor levels and cerebral microbleeds in patients with Alzheimer's disease

Abstract: Serum VEGF levels are associated with the presence of CMBs in patients with AD.

Cited by 24 publications

References 36 publications

Blood-Brain Barrier Dysfunction in Small Vessel Disease Related Intracerebral Hemorrhage

Blood-Brain Barrier Dysfunction in Small Vessel Disease Related Intracerebral Hemorrhage

Genetic resilience to amyloid related cognitive decline

Vascular Endothelial Growth Factor remains unchanged in cerebrospinal fluid of patients with Alzheimer’s disease and vascular dementia

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