VEGF and ICAM5 Levels in Alzheimer’s Disease and Cognitively Healthy Aging
Bibliographic record
Abstract
BACKGROUND: Vascular dysfunction, blood-brain barrier (BBB) dysregulation, and neuroinflammation are thought to participate in Alzheimer`s disease (AD) pathogenesis, though the mechanism is poorly understood. Among pathways of interest, AD pathology appears to affect vascular endothelial growth factor-A (VEGFA) signaling in a bidirectional manner. Higher VEGF levels are thought to have a protective role and slow cognitive decline. Neuronal intracellular adhesion molecules (ICAMs) may also be a marker of BBB permeability. ICAMs participate in the immune-nervous system interactions, synaptic plasticity, and cognition. METHOD: We used the SomaLogic platform for cerebrospinal fluid (CSF) proteome profiling to investigate the levels of ICAM 1, 2, 3, 5 and VEGFA as markers of vascular dysfunction and neuroinflammation in 83 participants from the Stanford Alzheimer Disease Research Center cohort (54 cognitively unimpaired healthy controls (HC) and 29 with mild cognitive impairment or dementia due to AD). All samples were blinded for analysis. Montreal Cognitive Assessment (MoCA) was used as a measure of global cognition. ANOVA compared the levels of biomarkers in diagnostic groups. Linear regression and interaction terms of group (AD vs HC) by biomarker levels were used to investigate the effect on global cognition. RESULT: ICAM5 and VEGFA were significantly associated with cognition in our cohort. Both ICAM5 and VEGFA levels were lower in AD compared to HC (Figure 1). Interaction terms of diagnosis by ICAM5 were significant on MoCA (b = -59.29, p-value < .0001), and of diagnosis by VEGFA were also significant on MoCA (b = -134.8, p:0.00027), indicating a divergent role for these biomarkers in AD vs. HC (Figure 2). Other ICAMs were not significantly associated with cognition in our cohort. CONCLUSION: VEGFA and ICAM5 may play an important and dynamic role in AD. More research is needed to understand the interplay between ICAM5 and VEGF and their relationship with AD. References: Tao QQ et al. Aging Dis. 2022; Tubi MA et al. Neurobiol Aging. 2021; Petrelis AM et al. Aging (Albany NY). 2022; Yuan L et al. Aging Dis. 2017; Hino H et al. Brain Res. 1997; Yang H. Comp Funct Genomics. 2012; Birkner K et al. Front Neurol. 2019.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".