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Angiogenic factors in biofluids show no significant difference in Alzheimer's diseaseComparing blood markers to see if they help identify Alzheimer disease

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Key Takeaway
Interpret angiogenic factor levels in biofluids as not significantly different between Alzheimer's disease and normal aging.

This systematic review and meta-analysis of 18 studies (including 28 dependent effect sizes) examined differences in angiogenic biomarker levels in biofluids between individuals with Alzheimer's disease and healthy older adults. The primary outcome was the overall effect size of angiogenic factors, which was small and nonsignificant (Hedges' g = -0.26, 95% CI [-1.45, 0.92], p = 0.647). A moderator analysis comparing VEGF versus other angiogenic biomarkers also found no significant difference.

Significant heterogeneity was observed (I² = 98.6%, p < 0.0001), indicating substantial variability across studies. The authors note that this heterogeneity limits the reliability of the pooled estimate. The analysis is based on observational or cross-sectional data, so only associations can be inferred, not causality.

The practice relevance lies in the potential for identifying novel angiogenic biomarkers to elucidate vascular mechanisms in Alzheimer's disease and reveal therapeutic targets. However, the current evidence does not support a significant difference in angiogenic factor levels between Alzheimer's patients and healthy controls.

How this fits prior evidence

This meta-analysis extends prior findings on Alzheimer's disease biomarkers, such as the identification of 194 miRNAs linked to Alzheimer's disease and EEG microstate differences in AD. However, unlike those markers, angiogenic factors in biofluids showed no significant difference between AD and healthy controls. The high heterogeneity contrasts with more consistent findings in other biomarker studies, suggesting that angiogenic factors may not be robust discriminators.

Scientists studied a large group of reports to see if certain proteins, called angiogenic factors, show up differently in people with Alzheimer's disease. These specific proteins are usually involved in growing new blood vessels in the body.

The goal was to see if measuring these levels in fluids like blood could help doctors identify the disease earlier or understand how it affects blood vessels. They looked at several different types of these markers, including one very common type called VEGF.

The results showed that there was no clear difference in these protein levels between people with Alzheimer's and healthy older adults. Even when looking specifically at the most common marker, the levels were similar across both groups.

Because the results were not significant, these specific markers may not be reliable tools for diagnosing the disease right now. However, studying these proteins helps scientists better understand how blood vessels and brain health are connected.

What this means for you:
Current research shows that these specific blood protein levels do not clearly distinguish Alzheimer's from normal aging.

Common questions

What are angiogenic factors?

Angiogenic factors are proteins, such as VEGF and fibroblast growth factor, that help the body grow new blood vessels. Researchers studied these in biofluids to see if they could help explain how vascular issues might relate to Alzheimer's disease.

Did the study find a link between these markers and Alzheimer's?

The analysis of 18 studies found a small and non-significant overall effect size for these factors. This means there was no clear difference in biomarker levels between people with Alzheimer's disease and healthy older adults.

Was the finding specific to any one type of marker?

No, the study found that there was no significant difference based on which specific angiogenic biomarker was examined. This includes VEGF compared to other types of angiogenic biomarkers in the samples tested.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedJul 2026
View Original Abstract ↓
BackgroundCerebrovascular dysfunction can contribute to the pathophysiology of Alzheimer's disease (AD) and trigger angiogenesis. To date, no prior systematic review and meta-analysis (SRMA) study has attempted to qualitatively and quantitatively review existing literature examining angiogenic factors in AD.ObjectiveIn this review, we aimed to identify markers of angiogenesis in biofluids that can differentiate between individuals with AD and healthy older adults, and inform the role of angiogenesis in AD.MethodsUsing Medline (1946 to August 4, 2021), the literature was systematically searched for articles according to PRISMA guidelines. Angiogenesis and AD terms were searched as keywords and mapped to MeSH headings. A total of 18 studies (including 28 dependent effect sizes) were included in the meta-analysis. Hedges' g was selected as the effect size of interest.ResultsA random-effects model including all eligible biofluid studies revealed a small and nonsignificant overall effect size (combined Hedges' g = -0.26, 95% CI [-1.45, 0.92], p = 0.647), with significant heterogeneity (I = 98.6%, p < 0.0001). Moderator analysis revealed no significant difference based on which specific angiogenic biomarker was examined (i.e., vascular endothelial growth factor (VEGF) versus others).ConclusionsVEGF-related marker levels were not significantly different in AD and normal aging. Based on our findings, few studies have examined fibroblast growth factor and platelet-derived growth factor-related markers; however, we believe they warrant further investigation. Identifying novel angiogenic biomarkers could elucidate the role of vascular mechanisms in AD and reveal potential therapeutic targets.
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