Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer’s dementia

Abstract

Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured and correlated with the cognitive performance, white matter macro-structural changes, and major tract-specific fractional anisotropy quantification. The AD patients were further stratified by clinical dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50). Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028) and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM-1 levels significantly reflected the severity of dementia (p< 0.001). In addition, only VCAM-1 levels showed an association with macro- and micro- white matter changes especially in the superior longitudinal fasciculus (p< 0.001), posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus callosum (p=0.009), and were independent of, age and cortical volume. These tracts show significant association with MMSE, short term memory and visuospatial function. Meanwhile, while VCAM-1 level correlated significantly with short-term memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting for age and education, the significance disappeared after adjusting for global FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD that reflects macro- and micro-structural changes and poor short term memory and visuospatial function.

Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

“…Neuroinflammation is thought to contribute to the pathogenesis of AD, with active central nervous system trafficking of immunoregulatory cells necessary for amyloid clearance and mitigation of the neuroinflammatory response [34]. IL-6 and IL-12 (which can be regulated by IL-1; [35]) have been proposed as the most significant contributors to inflammatory response in LOAD [36, 37], and VCAM-1 has been associated with white-matter integrity and cognitive performance in AD [38, 39]. Both RORA and SIRT1 are part of the biological-clock gene machinery and have been linked to circadian control of gene expression [40].…”

Differential Peripheral Inflammatory Factors Associated with Cognitive Function in Patients with Heart Failure

“…We assessed biomarkers known to be involved in cerebro- and/or cardiovascular disease, and cognitive impairment: interferon-γ (IFNγ), TNFα, sICAM-1, sVCAM-1, BDNF, IL-8, matrix metallopeptidase-9 (MMP-9), IL-6, CRP, and SAA [11, 13, 15, 19, 22]. After a 10-min rest period, whole blood was drawn into a 10-mL vacutainer tube preserved with EDTA while participants were in an upright sitting position.…”

“…However, for 1,284 participants in the Longitudinal Aging Study Amsterdam, there was no association between cognitive decline and serum levels of IL-6 [12]. Immune factors associated with vascular disease, soluble vascular cell adhesion molecule-1 (sVCAM-1) ( p < 0.001) and soluble intercellular adhesion molecule-1 (sICAM-1) ( p = 0.028) were higher in patients with dementia, and sVCAM-1 levels corresponded with the dementia severity, macro- and micro-white matter changes, poor short-term memory, and visuospatial function [13]. Additionally, tumor necrosis factor-α (TNFα) was observed to be higher in vascular dementia than in late-onset Alzheimer’s disease (AD), whereas IL-6 was higher in AD [14].…”

Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer’s disease

“…The presence of WMHs in AD may reflect multiple physiological and pathological changes such as breakdown of the blood-brain barrier [20], impaired cerebral auto-regulation [21], vasculopathies, and inflammation [22, 23]. In healthy adults, homozygotes for the IL-1 beta -511 T allele have been associated with increased inflammatory responses and larger WMHs than the other two genotypic combinations [24].…”