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

Abstract

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.

Biomarkers Related to Endothelial Dysfunction and Vascular Cognitive Impairment: A Systematic Review

“…In contrast, Chakraborty et al [30] found no significant difference in CSF VEGF levels across patients with VaD, AD, and controls. Ke et al [28] also did not find significant differences in intrathecal levels of VEGF or BNDF in patients with ischemic cerebrovascular diseases and VCI compared with controls.…”

“…Overall, these inconsistent results suggest that angiogenic factors may play a yet incompletely understood role in multiple forms of dementia, including vascular and neurodegenerative pathologies. Studies with VEGF CSF levels in AD populations have also yielded inconsistent results [29, 30, 34].…”

Berberine Improves Cognitive Impairment by Simultaneously Impacting Cerebral Blood Flow and β-Amyloid Accumulation in an APP/tau/PS1 Mouse Model of Alzheimer’s Disease

“…The impact of VEFG also reflects the pathological progress of AD. A negative correlation between the level of VEGF and the development progress of AD’s pathological process has been observed [ 35 ]. VEGF can act directly on many types of nerve cells to play a neurotrophic and neuroprotective role, enhance cell activity and survival, and promote axon regeneration.…”

Inhibition of peripheral VEGF signaling rapidly reduces leucocyte obstructions in brain capillaries and increases cortical blood flow in an Alzheimer’s disease mouse model

“…Several studies have explored the role of VEGF-A signaling in patients with AD. Most studies find increased levels of VEGF-A in the serum or CSF of patients with AD ( 18, 43–45 ), with a minority showing reduced ( 22, 46 ) or unchanged levels ( 47 ). Increased VEGF-A levels are also seen in brain homogenates from the TgCNDR8 ( 48 ) and APP/PS1 mouse models of AD ( 49 ), as well as in endothelial cells of arteries, veins, and capillaries from aged WT mice( 50 ), mouse models of APP over expression ( 24, 51 ), mutant Tau mice ( 52 ), and patients with AD ( 53–55 ).…”