Intermediate filaments (IFs) are key molecular factors of the cell and have been reported to play an important role in maintaining the structural integrity and functionality of the abomasum. This study was designed to determine the regional distribution, cellular localization and expression of several IFs, including CK8, CK18, CK19, vimentin, desmin, peripherin and nestin, as well as the connective tissue component laminin, in the bovine, ovine and caprine abomasa. Immunohistochemical analyses demonstrated varying levels of expression of CK8, CK18, CK19, vimentin, desmin, nestin, peripherin and laminin in the bovine, ovine and caprine abomasa. CK8 immunoreactions were particularly evident in the luminal and glandular epithelia of the glands found in the abomasal cardia, fundus and pylorus in all three species. In the bovine abomasum, CK18 immunoreactions were stronger in the parietal cells, compared to the chief cells. In the abomasum of all three species, the smooth muscle as well as the smooth muscle cells of the vascular media in the cardiac, fundic and pyloric regions showed strong immunoreactivity. In all three species, the cardiac, fundic and pyloric regions of the abomasum showed strong peripherin and nestin immunoreactions in the luminal and glandular epithelial cells, stromal and smooth muscle cells, nervous plexuses and blood vessels. The expression patterns of IFs and laminin in the ruminant abomasum suggest that these proteins play a structural role in the cytoskeleton and are effective in maintaining abomasal tissue integrity and stability.

The blood-based biomarkers are approaching the clinical practice of Alzheimer\'s disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers.
Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted.
The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001).
Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.

BACKGROUND: Smoke exposure is a prevalent and well-documented risk factor for various diseases across different organ systems. Serum neurofilament light chain (sNfL) has emerged as a promising biomarker for a multitude of nervous system disorders. However, there is a notable paucity of research exploring the associations between smoke exposure and sNfL levels.
METHODS: We conducted a comprehensive analysis of the National Health and Nutrition Examination Survey (NHANES) cross-sectional data spanning the years 2013 to 2014. Serum cotinine levels were classified into the following three groups: < 0.05, 0.05-2.99, and ≥ 3 ng/ml. Multiple linear regression models were employed to assess the relationships between serum cotinine levels and sNfL levels. Additionally, we utilized restricted cubic spline analyses to elucidate the potential nonlinear relationship between serum cotinine and sNfL levels.
RESULTS: A total of 2053 participants were included in our present research. Among these individuals, the mean age was 47.04 ± 15.32 years, and males accounted for 48.2% of the total study population. After adjusting the full model, serum cotinine was positively correlated with sNfl in the second group (β = 0.08, 95%CI 0.01-0.15) and in the highest concentration of serum cotinine (β = 0.10, 95%CI 0.01-0.19) compared to the group with the lowest serum cotinine concentrations. Current smokers, in comparison to non-smokers, exhibited a trend toward elevated sNfL levels (β = 0.07, 95%CI 0.01-0.13). Furthermore, subgroup analyses revealed interactions between serum cotinine levels and different age groups (P for interaction = 0.001) and gender stratification (P for interaction = 0.015) on sNfL levels.
CONCLUSIONS: The study suggested that serum cotinine was significantly and positively associated with sNfl levels in adult participants. Furthermore, current smokers tend to exhibit elevated sNfL levels. This research sheds light on the potential implications of smoke exposure on neurological function impairment and underscores the importance of further exploration in this area.

Recent evidence suggests that blood-based biomarkers might be useful for Alzheimer\'s disease (AD). Among them, we intend to investigate whether neurofilament light (NfL) and multimer detection system-oligomeric Aβ (MDS-OAβ) values can be useful in screening, predicting, and monitoring disease progression and how the relationship between NfL and MDS-OAβ values changes.
Eighty participants with probable AD dementia, 50 with mild cognitive impairment (MCI), and 19 with subjective cognitive decline (SCD) underwent baseline and follow-up evaluations of the Mini-Mental Status Examination (MMSE) and both plasma biomarkers.
Baseline MDS-OAß (p = 0.016) and NfL (p = 0.002) plasma concentrations differed significantly among groups, but only NfL correlated with baseline MMSE scores (r = -0.278, p = 0.001). In follow-up, neither correlated with MMSE changes overall. However, in SCD and MCI participants (n = 32), baseline MDS-OAß correlated with follow-up MMSE scores (r = 0.532, p = 0.041). Linear regression revealed a relationship between baseline MDS-OAβ and follow-up MMSE scores. In SCD and MCI participants, plasma NfL changes correlated with MMSE changes (r = 0.564, p = 0.028).
This study shows that only in participants with SCD and MCI, not including AD dementia, can MDS-OAß predict the longitudinal cognitive decline measured by follow-up MMSE. Changes of NfL, not MDS-OAß, parallel the changes of MMSE. Further studies with larger samples and longer durations could strengthen these results..

BACKGROUND: Impaired cognition is a major predisposing factor for postoperative delirium, but it is not systematically assessed. Anesthesia and surgery may cause postoperative delirium by affecting brain integrity. Neurofilament light in serum reflects axonal injury. Studies evaluating the perioperative course of neurofilament light in cardiac surgery have shown conflicting results. The authors hypothesized that postoperative serum neurofilament light values would be higher in delirious patients, and that baseline concentrations would be correlated with patients\' cognitive status and would identify patients at risk of postoperative delirium.
METHODS: This preplanned secondary analysis included 220 patients undergoing elective cardiac surgery with cardiopulmonary bypass. A preoperative cognitive z score was calculated after a neuropsychological evaluation. Quantification of serum neurofilament light was performed by the Simoa (Quanterix, USA) technique before anesthesia, 2 h after surgery, on postoperative days 1, 2, and 5. Postoperative delirium was assessed using the Confusion Assessment Method for Intensive Care Unit, the Confusion Assessment Method, and a chart review.
RESULTS: A total of 65 of 220 (29.5%) patients developed postoperative delirium. Delirious patients were older (median [25th percentile, 75th percentile], 74 [64, 79] vs. 67 [59, 74] yr; P < 0.001) and had lower cognitive z scores (-0.52 ± 1.14 vs. 0.21 ± 0.84; P < 0.001). Postoperative neurofilament light concentrations increased in all patients up to day 5, but did not predict delirium when preoperative concentrations were considered. Baseline neurofilament light values were significantly higher in patients who experienced delirium. They were influenced by age, cognitive z score, renal function, and history of diabetes mellitus. Baselines values were significantly correlated with cognitive z scores (r, 0.49; P < 0.001) and were independently associated with delirium whenever the patient\'s cognitive status was not considered (hazard ratio, 3.34 [95% CI, 1.07 to 10.4]).
CONCLUSIONS: Cardiac surgery is associated with axonal injury, because neurofilament light concentrations increased postoperatively in all patients. However, only baseline neurofilament light values predicted postoperative delirium. Baseline concentrations were correlated with poorer cognitive scores, and they independently predicted postoperative delirium whenever patient\'s cognitive status was undetermined.
UNASSIGNED:

BACKGROUND: Neurofilament light is a blood-based biomarker of neuroaxonal injury that can provide insight into perioperative brain vulnerability and injury. Prior studies have suggested that increased baseline and postoperative concentrations of neurofilament light are associated with delirium after noncardiac surgery, but results are inconsistent. Results have not been reported in cardiac surgery patients, who are among those at highest risk for delirium. We hypothesised that perioperative blood concentrations of neurofilament light (both baseline and change from baseline to postoperative day 1) are associated with delirium after cardiac surgery.
METHODS: This study was nested in a trial of arterial blood pressure targeting during cardiopulmonary bypass using cerebral autoregulation metrics. Blood concentrations of neurofilament light were measured at baseline and on postoperative day 1. The primary outcome was postoperative delirium. Regression models were used to examine the associations between neurofilament light concentration and delirium and delirium severity, adjusting for age, sex, race, logistic European System for Cardiac Operative Risk Evaluation, bypass duration, and cognition.
RESULTS: Delirium occurred in 44.6% of 175 patients. Baseline neurofilament light concentration was higher in delirious than in non-delirious patients (median 20.7 pg ml-1 [IQR 16.1-33.2] vs median 15.5 pg ml-1 [IQR 12.1-24.2], P<0.001). In adjusted models, greater baseline neurofilament light concentration was associated with delirium (odds ratio, 1.027; 95% confidence interval, 1.003-1.053; P=0.029) and delirium severity. From baseline to postoperative day 1, neurofilament light concentration increased by 42%, but there was no association with delirium.
CONCLUSIONS: Baseline neurofilament light concentration, but not change from baseline to postoperative day 1, was associated with delirium after cardiac surgery.

OBJECTIVE: Rasagiline might be disease modifying in patients with amyotrophic lateral sclerosis (ALS). The aim was to evaluate the effect of rasagiline 2 mg/day on neurofilament light chain (NfL), a prognostic biomarker in ALS.
METHODS: In 65 patients with ALS randomized in a 3:1 ratio to rasagiline 2 mg/day (n = 48) or placebo (n = 17) in a completed randomized controlled multicentre trial, NfL levels in plasma were measured at baseline, month 6 and month 12. Longitudinal changes in NfL levels were evaluated regarding treatment and clinical parameters.
RESULTS: Baseline NfL levels did not differ between the study arms and correlated with disease progression rates both pre-baseline (r = 0.64, p < 0.001) and during the study (r = 0.61, p < 0.001). NfL measured at months 6 and 12 did not change significantly from baseline in both arms, with a median individual NfL change of +1.4 pg/mL (interquartile range [IQR] -5.6, 14.2) across all follow-up time points. However, a significant difference in NfL change at month 12 was observed between patients with high and low NfL baseline levels treated with rasagiline (high [n = 13], -6.9 pg/mL, IQR -20.4, 6.0; low [n = 18], +5.9 pg/mL, IQR -1.4, 19.7; p = 0.025). Additionally, generally higher longitudinal NfL variability was observed in patients with high baseline levels, whereas disease progression rates and disease duration at baseline had no impact on the longitudinal NfL course.
CONCLUSIONS: Post hoc NfL measurements in completed clinical trials are helpful in interpreting NfL data from ongoing and future interventional trials and could provide hypothesis-generating complementary insights. Further studies are warranted to ultimately differentiate NfL response to treatment from other factors.

OBJECTIVE: Serum neurofilament light chain (sNfL) can reflect nerve damage. Whether migraine can cause neurological damage remain unclear. This study assesses sNfL levels in migraine patients and explores whether there is nerve damage in migraine.
METHODS: A case-control study was conducted in Xiamen, China. A total of 138 migraine patients and 70 healthy controls were recruited. sNfL (pg/mL) was measured on the single-molecule array platform. Univariate, Pearson correlation and linear regression analysis were used to assess the relationship between migraine and sNfL levels, with further subgroup analysis by migraine characteristics.
RESULTS: Overall, 85.10% of the 208 subjects were female, with a median age of 36 years. sNfL levels were higher in the migraine group than in the control group (4.85 (3.49, 6.62) vs. 4.11 (3.22, 5.59)), but the difference was not significant (P = 0.133). The two groups showed an almost consistent trend in which sNfL levels increased significantly with age. Subgroup analysis showed a significant increase in sNfL levels in patients with a migraine course ≥ 10 years (β = 0.693 (0.168, 1.220), P = 0.010). Regression analysis results show that age and migraine course are independent risk factors for elevated sNfL levels, and there is an interaction between the two factors. Patients aged < 45 years and with a migraine course ≥ 10 years have significantly increased sNfL levels.
CONCLUSIONS: This is the first study to evaluate sNfL levels in migraine patients. The sNfL levels significantly increased in patients with a migraine course ≥ 10 years. More attention to nerve damage in young patients with a long course of migraine is required.

Reactive astrogliosis has been demonstrated to have a role in Parkinson\'s disease (PD); however, astrocyte-specific plasma glial fibrillary acidic protein (GFAP)\'s correlation with PD progression remains unknown. We aimed to determine whether plasma GFAP can monitor and predict PD progression.
A total of 184 patients with PD and 95 healthy controls (HCs) were included in this prospective cohort study and followed-up for 5 years. Plasma GFAP, amyloid-beta (Aβ), p-tau181, and neurofilament light chain (NfL) were measured at baseline and at 1- and 2-year follow-ups. Motor and non-motor symptoms, activities of daily living, global cognitive function, executive function, and disease stage were evaluated using the Unified Parkinson\'s Disease Rating Scale (UPDRS) part III, UPDRS-I, UPDRS-II, Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), and Hoehn and Yahr (H&Y) scales at each visit, respectively.
Plasma GFAP levels were higher in patients with PD (mean [SD]: 69.80 [36.18], pg/mL) compared to HCs (mean [SD]: 57.89 [23.54], pg/mL). Higher levels of GFAP were observed in female and older PD patients. The adjusted linear mixed-effects models showed that plasma GFAP levels were significantly associated with UPDRS-I scores (β: 0.006, 95% CI [0.001-0.011], p = 0.027). Higher baseline plasma GFAP correlated with faster increase in UPDRS-I (β: 0.237, 95% CI [0.055-0.419], p = 0.011) and UPDRS-III (β: 0.676, 95% CI [0.023-1.330], p = 0.043) scores and H&Y stage (β: 0.098, 95% CI [0.047-0.149], p < 0.001) and faster decrease in MoCA (β: - 0.501, 95% CI [- 0.768 to - 0.234], p < 0.001) and FAB scores (β: - 0.358, 95% CI [- 0.587 to - 0.129], p = 0.002). Higher baseline plasma GFAP predicted a more rapid progression to postural instability (hazard ratio: 1.009, 95% CI [1.001-1.017], p = 0.033).
Plasma GFAP might be a potential biomarker for monitoring and predicting disease progression in PD.

Early identification of cognitive impairment in neurodegenerative diseases like Alzheimer\'s disease (AD) is crucial. Neurofilament, a potential biomarker for neurological disorders, has gained attention. Our study aims to investigate the relationship between serum neurofilament light (sNfL) levels and cognitive function in elderly individuals in the United States.
This cross-sectional study analyzed data from participants aged 60 and above in the National Health and Nutrition Examination Survey (2013-2014). We collected sNfL levels, cognitive function tests, sociodemographic characteristics, comorbidities, and other variables. Weighted multiple linear regression models examined the relationship between ln(sNfL) and cognitive scores. Restricted cubic spline (RCS) visualization explored nonlinear relationships. The stratified analysis examined subgroups\' ln(sNfL) and cognitive function association.
The study included 446 participants (47.73% male). Participants with ln(sNfL) levels between 2.58 and 2.81 pg/mL (second quintile) performed relatively well in cognitive tests. After adjusting for multiple factors, ln(sNfL) levels were negatively correlated with cognitive function, with adjusted β (95% CI) as follows: immediate recall test (IRT): -0.763 (-1.301 to -0.224), delayed recall test (DRT): -0.308 (-0.576 to -0.04), animal fluency test (AFT): -1.616 (-2.639 to -0.594), and digit symbol substitution test (DSST): -2.790 (-4.369 to -1.21). RCS curves showed nonlinear relationships between ln(sNfL) and DRT, AFT, with inflection points around 2.7 pg/mL. The stratified analysis revealed a negative correlation between ln(sNfL) and cognition in specific subgroups with distinct features, with an interaction between diabetes and ln(sNfL).
Higher sNfL levels are associated with poorer cognitive function in the elderly population of the United States. sNfL shows promise as a potential biomarker for early identification of cognitive decline.