Gender-Dependent Levels of Hyaluronic Acid in Cerebrospinal Fluid of Patients with Neurodegenerative Dementia

Abstract

Numerous reports over the years have described neuroinflammatory events and vascular changes in neurodegenerative diseases such as Alzheimer´s disease (AD) and dementia with Lewy bodies (DLB). Interestingly, recent reports from other research areas suggest that inflammatory and vascular processes are influenced by gender. These findings are intriguing from the perspective that women show a higher incidence of AD and warrant investigations on how gender influences various processes in neurodegenerative dementia. In the current study we measured the cerebrospinal fluid (CSF) and plasma concentrations of hyaluroinic acid (HA), an adhesionmolecule known to regulate both vascular and inflammatory processes, in AD and DLB patients as well as in healthy elders. Our analysis showed that male AD and DLB patients had almost double the amount of HA compared to female patients whereas no gender differences were observed in the controls. Furthermore, we found that CSF levels of HA in foremost female AD patients correlated with various AD related biomarkers. Correlations between HA levels and markers of inflammation and vascular changes were only detected in female AD patients but in both male and female DLB patients. We conclude that HA may be linked to several pathological events present in AD, as reflected in CSF protein concentrations. The HA profile in CSF, but not in plasma, and associations to other markers appear to be genderdependent which should be taken into account in clinical examinations and future biomarker studies.

The neuropathology and cerebrovascular mechanisms of dementia

“…Consistently, reports of CSF and plasma concentrations of hyaluroinic acid, an adhesion molecule known to regulate both vascular and inflammatory processes, was found to be higher in patients with DLB as compared with cognitively normal and age-matched controls. 50 Taken together, these data suggest that DLB patients experience a robust inflammatory response and vascular abnormalities, which further exacerbate Lewy body-induced neuropathology.…”

Increased Levels of Hyaluronic Acid in Cerebrospinal Fluid in Patients with Vascular Dementia

“…Studies performed by us and others have demonstrated increased levels of HA in CSF from individuals with pathologic changes in the brain vasculature [9,10]. In the current study, we aimed to investigate whether the level of HA in CSF could function as a clinical diagnostic marker for VaD and thus we measured HA levels in a new patient cohort consisting of patients clinically diagnosed with AD and VaD and controls without dementia.…”

“…Increased levels of HA in CSF from stroke patients have been reported [9]. In addition, we have recently demonstrated increased levels of HA in CSF from patients with Alzheimer's disease (AD) with vascular changes and a strong correlation between the levels of HA in CSF and Q-albumin (CSF/serum albumin ratio), an indicator of the function of the blood-brain barrier (BBB) [10]. To further investigate the potential diagnostic value of HA for vascular dementia (VaD), in this study we analyze HA in a new patient cohort consisting of controls without dementia and patients with AD and VaD.…”

“…Levels of shedded soluble HA can be measured in blood and cerebrospinal fluid (CSF) [9][10][11] and could thus theoretically function as a diagnostic marker reflecting glycocalyx degradation and vascular dysfunction. Increased levels of HA in CSF from stroke patients have been reported [9].…”

Cell adhesion molecules in Alzheimer's disease

“…In a recent study we also showed that CSF levels of ICAM-1 in female AD patients correlated with levels of hyaluronic acid, an adhesion molecule implicated in both inflammatory events and vascular changes. 97 The main significance of the described altered levels of Ig-CAMs in AD requires further investigation as neuroinflammation in AD appears to take place without any apparent influx of leukocytes from the blood. 98 Thus, the altered levels of the soluble forms of Ig-CAMs may reflect inflammatory processes unrelated to cognitive performance (as assessed with MMSE).…”