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

Numerous reports over the years have described neuroinflammatory events and vascular changes in neurodegenerative diseases such as Alzheimers 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 gender-dependent which should be taken into account in clinical examinations and future biomarker studies. Keywords: Alzheimer's disease, Dementia with Lewy bodies, gender, hyaluronic acid, inflammation, vascular changes