Elevated cerebrospinal fluid biomarkers of neuroinflammation and neuronal damage in essential hypertension with secondary insomnia: Implications for Alzheimer's disease risk

Abstract

Essential hypertension (EH) with secondary insomnia is associated with increased risks of neuroinflammation, neuronal damage, and Alzheimer's disease (AD). However, its relationship with specific cerebrospinal fluid (CSF) biomarkers of neuronal damage and neuroinflammation remains unclear. This case-control study compared CSF biomarker levels across three groups: healthy controls (HC, n = 64), hypertension-controlled (HTN-C, n = 54), and hypertension-uncontrolled (HTN-U, n = 107) groups, all EH participants experiencing secondary insomnia. CSF samples from knee replacement patients were analyzed for key biomarkers, and sleep quality was assessed via the Pittsburgh Sleep Quality Index (PSQI). Our findings showed that the HTN-U group had significantly higher CSF levels of proinflammatory cytokines IL-6, TNF-α, and IL-17 than the HC and HTN-C groups (all p < 0.01). These cytokines correlated positively with secondary insomnia measures, with IL-6 (r = 0.285, p = 0.003), IL-17 (r = 0.324, p = 0.001), and TNF-α (r = 0.274, p = 0.005) linked to PSQI scores. In the HTN-U group, elevated IL-6, TNF-α, and IL-17 levels were also positively associated with neurofilament light (NF-L) and negatively with β-amyloid 42 (Aβ42), both key AD markers (all p < 0.05). Additionally, secondary insomnia was negatively correlated with Aβ42 (r = -0.225, p = 0.021) and positively with NF-L (r = 0.261, p = 0.007). Higher CSF palmitic acid (PA) levels observed in the HTN-U group were linked to poorer sleep quality (r = 0.208, p = 0.033). In conclusion, EH with secondary insomnia is associated with CSF biomarkers of neuronal damage, neuroinflammation, and neurodegeneration, suggesting a potential increase in AD risk among this population.

Keywords: Alzheimer’s disease; Cerebrospinal fluid; Essential hypertension; Insomnia.