Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders

Abstract

Clearance of neurotoxic brain proteins via cerebrospinal fluid (CSF) to blood has recently emerged to be crucial, and plasma biomarkers of neurodegeneration were newly introduced to predict neurological disease. This study examines in 106 individuals with neurological disorders associations between plasma biomarkers [40 and 42 amino acid-long amyloid-β (Aβ40 and Aβ42), total-tau, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL)] and magnetic resonance imaging measures of CSF-mediated clearance from brain via extra-vascular pathways (proxy of glymphatic function) and CSF-to-blood clearance variables from pharmacokinetic modeling (proxy of meningeal lymphatic egress). We also examine how biomarkers vary during daytime and associate with subjective sleep quality. Plasma concentrations of neurodegeneration markers associate with indices of glymphatic and meningeal lymphatic functions in individual- and disease-specific manners, vary during daytime, but are unaffected by sleep quality. The results suggest that plasma concentrations of neurodegeneration biomarkers associate with measures of glymphatic and meningeal lymphatic function.

Sleep and APOE‐ε4 have a synergistic effect on plasma biomarkers and longitudinal cognitive decline in older adults

“…Plasma biomarker concentrations appear to be influenced by underlying diseases. 44 In our study, we observed that plasma NfL was significantly higher in the SCI+ group compared to the SCIgroup. Within the SCI+ group, we also found a significant nega- previous cross-sectional study, although they measured Aβ42/40 using CSF.…”

“…Plasma biomarker concentrations appear to be influenced by underlying diseases 44 . In our study, we observed that plasma NfL was significantly higher in the SCI+ group compared to the SCI‐ group.…”

Plasmodium knowlesiinfection is associated with elevated circulating biomarkers of brain injury and endothelial activation

“…In our study, several biomarkers were significantly decreased in Pk -infected individuals compared to healthy controls, including GFAP, BDNF, CaBD, CNTN1, NCAM-1, and KLK6. The astrocytic intermediate filament protein GFAP, used in clinical settings to assess severity of traumatic brain injury (49), glymphatic function (50), and neurodegeneration (51,52), was not found to be elevated in Ugandan children with falciparum cerebral malaria and severe malarial anemia (44). In contrast, the observed differences in GFAP levels in our groups may suggest altered astroglial and/or glymphatic functions in infected participants, supporting our hypothesis of cerebral involvement in Pk malaria.…”

Predictive Modeling Using a Composite Index of Sleep and Cognition in the Alzheimer’s Continuum: A Decade-Long Historical Cohort Study

“…Although this statistically significant association was only observed in one sleep duration group (6–7 h), it remained present in the analysis using dichotomous sleep durations (>7 h versus < 7 h) [ 30 ]. However, some studies came up with different evidence: no significant correlation was found between total PSQI score and plasma biomarker concentrations, and there was no significant difference in plasma biomarker concentrations between good (PSQI total score≤5) and poor (PSQI total score > 6) sleep quality [ 31 ]. In the research of AD and RBDSQ, a previous study found that smaller pineal parenchymal volume in AD patients is associated with increased symptoms of RBD (assessed by RBDSQ) [ 32 ].…”

“…Considering previous studies, there is a lack of evidence indicating peripheral Aβ peptides change in response to sleep deprivation, suggesting that measurements of peripheral Aβ biomarkers may be less accurate in reflecting changes in the central nervous system due to sleep deprivation. In another study, plasma concentrations of T-tau, GFAP, and NfL increased during the day and T-tau decreased significantly at night, suggesting the clearance during sleep, possibly through lymphatic fluid or CSF, although different changes in the said biomarkers were observed in other cohorts [ 31 ]. The above evidence suggests that certain AD biomarkers exhibit diurnal variation that may be independent of sleep, providing theoretical support to use SCI to reflect the combination of daytime and nighttime conditions.…”