Search Results (325)

Interleukin 17 (IL-17) is a crucial mediator at the interface of periodontal dysbiosis and host immunity. This review synthesizes current evidence on IL-17 in periodontitis (PD), its systemic connections, and the role of IL-17 gene variants. Clinical and experimental studies show that IL-17 rises in periodontal disease and is associated with the severity of PD via action on epithelial, stromal and osteoblastic cells to promote chemokine release, neutrophil recruitment, cyclooxygenase 2 and prostaglandin E2 synthesis, RANKL expression, osteoclastogenesis, and matrix metalloproteinase activity. Periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans pre-activate the local inflammation-maintaining Th17 response. There is converging evidence linking IL-17-centered signaling with rheumatoid arthritis, diabetes mellitus, and psoriasis in favor of a shared inflammatory network in barrier tissues and synovium. Despite these associations, IL-17 biology is contextually determined with mucosal defense and bone homeostatic roles that caution against unidimensional explanations. Evidence on IL-17A and IL-17F polymorphisms is still heterogeneous across populations with modest and variable risk associations with PD. Clinically, IL-17 in gingival crevicular fluid, saliva, or serum is a potential monitoring biomarker when utilized along with conventional indices. Therapeutically, periodontal therapy that reduces microbial burden may inhibit IL-17 function, and IL-17-targeted therapy has to balance potential benefit to inflammation and bone resorption against safety in oral tissues. The following research must utilize harmonized case definitions, standardized sampling, and multiethnic cohorts, and it must include multiomics to be able to differentiate between causal and compensatory IL-17 signals. Full article

Alcohol-associated liver disease is a global health burden with high morbidity and mortality, and the fungal microbiome is important for its progression. In particular, Candida albicans and C. albicans-reactive T helper 17 (Th17) cells contribute to alcohol-associated liver disease. Specific C. albicans antigens that activate Th17 cells during this disease are unknown. The C. albicans 65 kDa mannoprotein (CaMp65p) is one of the most abundant and immunodominant proteins of C. albicans, and is capable of eliciting robust T cell and interleukin (IL)-17A responses. The aim of this study was to measure levels of CaMp65p in serum of patients with alcohol use disorder and liver disease. Serum CaMp65p levels were measured in the serum of 60 patients with alcohol use disorder using an indirect competitive Enzyme-Linked Immunoabsorbent Assay (ELISA). Serum CaMp65p levels were correlated with liver disease severity. Serum CaMp65p levels positively correlated with several clinical and biochemical markers of liver injury and disease within the patient group with alcohol use disorder, including serum aspartate aminotransferase (AST; R = 0.33, p = 0.0092), alanine aminotransferase (ALT; R = 0.27, p = 0.037), gamma-glutamyl transferase (GGT; R = 0.35, p = 0.0055) and alkaline phosphatase (R = 0.36, p = 0.0052), and with the circulating M65 fragment of cytokeratin 18 (CK18-M65; R = 0.51, p = 0.0012), a marker of hepatocyte death. In addition, patients with alcohol use disorder in the upper quartile had significantly higher liver stiffness (p = 0.0022). Serum CaMp65p was significantly higher in patients with fibrosis stage F2–F4 as compared with patients with no or minimal fibrosis F0–F1 (p = 0.0082). The area under the curve (AUC) for detecting F2–F4 fibrosis was 0.70. Elevated serum CaMp65p levels are associated not only with more severe hepatic injury, but also with liver fibrosis in patients with alcohol use disorder. Therefore, CaMp65p may serve as a non-invasive biomarker for fibrosis assessment in patients with alcohol use disorder. Full article

Background: Cytokines participate in regulating the immune response of lymphocytes. Interleukin 2 (IL-2) is the main modulator of T lymphocyte development, homeostasis, and function, whereas interleukin 7 (IL-7) regulates the development and homeostasis of immune cells and plays a crucial role in the maintenance of memory cells. The study aims to assess the blood IL-2 and IL-7 concentration in relation to the obtained cellular and humoral response in adults, six months after vaccination against COVID-19. Methods: We measured the concentration of IL-2 and IL-7 with ELISA, CoV2-IgG with an indirect chemiluminescence test, and the levels of IFN-γ with interferon gamma release assay (IGRA) post SARS-CoV-2 antigen stimulation. The study group (n = 76; F = 66, M = 10) was divided into 41 individuals, who did not report any chronic disorder (ChrD-Neg), and 35, who did (ChrD-Pos). Results: ChrD-Pos group presented higher IL-7 compared to ChrD-Neg (p = 0.023). Negative correlations were observed in the entire study population between IL-2 and age (R = −0.252, p = 0.028), as well as between IL-7 and IFN-γ (R = −0.295, p = 0.010). We found a positive correlation between IL-2 and IL-7 concentrations in the entire study population (R = 0.305, p = 0.007) and the ChrD-Pos group (R = 0.358, p = 0.035), and people with a positive IGRA result (R = 0.359, p = 0.005). Conclusions: The interaction of IL-2 and IL-7 may be important for achieving post-vaccination immunity, especially in adults with chronic diseases. Age is a factor modifying the post-vaccination response (decreased IL-2), whereas IL-7 may be an important factor in achieving a satisfactory post-vaccine response in people with chronic diseases. Full article

Background: Psoriasis is a chronic inflammatory disease that frequently affects difficult-to-treat areas such as the scalp, nails, genitalia, and palms/soles, with significant physical and psychological burden. Bimekizumab, a monoclonal antibody targeting both interleukin (IL)-17A and IL-17F, has shown rapid and durable efficacy in clinical trials, but real-world data in these subgroups remain limited. Methods: We performed a 52-week, single-center retrospective study including patients with psoriasis involving at least one difficult-to-treat area. Effectiveness was assessed using site-specific Physician’s Global Assessment (sc-PGA, f-PGA, sPGA-G, pp-PGA). The primary endpoint was the proportion of patients achieving a PGA 0/1 (clear or almost clear). Safety data were collected at each visit. Results: Eighty-five patients were included (61.8% male; mean age 48.1 years; mean Body Mass Index (BMI, 26.9 kg/m²). Difficult-to-treat areas involved were the scalp (70.6%), nails (41.2%), genitalia (27.1%), and palms/soles (24.7%). At week 52, sc-PGA 0/1 was achieved in 90.6% of patients, sPGA-G 0/1 in 81.3%, f-PGA 0/1 in 66.7%, and pp-PGA 0/1 in 87.5%. Mean PGA values progressively decreased across all sites. The most common adverse event was oral candidiasis (11.8%). Conclusions: Bimekizumab showed rapid, sustained, and clinically meaningful improvement across all difficult-to-treat areas with a favorable safety profile. Full article

This experiment investigated the effects of seaweed polysaccharide (SP) and seaweed enzymatic hydrolysate (SEH) on the growth performance, serum biochemical indices, antioxidant capacity, and intestinal function of Muscovy ducks. A total of 240 healthy 1 day female Muscovy ducks (48.85 ± 0.45 g) were randomly divided into 3 treatment groups, with 4 replicates per group and 20 ducks per replicate. The control (CON) group received a basic diet supplemented with 20 mL/kg of water, the SP group received a basic diet supplemented with 20 mL/kg of SP, and the SEH group received a basic diet supplemented with 20 mL/kg of SEH. The experimental period lasted for 28 d. The results indicate that, compared to the CON group, the average daily feed intake (ADFI) and feed to gain (F/G) of the SP and SEH groups of ducks significantly decreased at 28 d (p < 0.05). In the SP group, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as the concentrations of glucose (GLU), triglycerides (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), were significantly reduced (p < 0.05). In the SEH group, the activities of ALT and AST were also significantly lower (p < 0.05). Additionally, serum total antioxidant capacity (T-AOC) levels and superoxide dismutase (SOD) activity in the SEH group were significantly higher than those in the CON group (p < 0.05), while the malondialdehyde (MDA) content was significantly reduced (p < 0.05). Compared to the CON group, serum levels of immunoglobulin A (IgA), immunoglobulin G (IgG), interleukin-4 (IL-4), and interleukin-10 (IL-10) in the SP group were significantly increased (p < 0.05), whereas the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) were significantly decreased (p < 0.05). In the SP and SEH groups, the villus height (VH) and the villus height to crypt depth (V/C) of the Muscovy ducks significantly increased (p < 0.05), while the crypt depth (CD) significantly decreased (p < 0.05). A significant increase in the abundance of Barnesiella was observed in the SP and SEH groups (p < 0.05), whereas the abundances of UCG-005 and Romboutsia significantly decreased (p < 0.05). LEfSe analysis indicated that g__Bacillus and g__Veillonella were significantly abundant in the SP group (p < 0.05), while g__Coriobacteriaceae_UCG_002 was significantly abundant in the SEH group (p < 0.05). In summary, the addition of SP and SEH to the feed can promote the healthy growth of ducks by improving intestinal morphology, regulating the structure of intestinal microbiota, enhancing antioxidant capacity and immune function, and optimizing metabolic indicators. This occurs while reducing feed intake and feed-to-weight ratio, and there is a certain specificity in their mechanisms of action. Full article

Prenatal maternal immune activation (MIA) has been implicated in autism spectrum disorder (ASD) pathogenesis, with interleukin-6 (IL-6) identified as a key inflammatory mediator. We investigated the therapeutic potential of IL-6 inhibition in an MIA mouse model induced by Toxoplasma gondii soluble tachyzoite antigen (STAg). Adult MIA offspring received systemic administration of the IL-6-neutralizing antibody (MP5-20F3) or isotype control, followed by behavioral assessments one week later. Open field and elevated plus maze tests revealed heightened anxiety-like behaviors in the STAg offspring, which were largely reversed by IL-6 inhibition. Reciprocal social interaction tests showed diminished sociability in the STAg offspring, which was partially restored by IL-6 inhibition. However, core ASD-like features, including impaired social preference and recognition in the three-chamber test, as well as increased repetitive behaviors, remained resistant to IL-6 inhibition. These findings demonstrate that STAg-induced MIA elicits anxiety-like and ASD-like phenotypes in adult offspring, with IL-6 playing an important role in anxiety-like behaviors and social interaction deficits. Systemic IL-6 inhibition partially ameliorates behavioral abnormalities. This study suggests that IL-6-targeted therapies may address a subset of ASD-related symptoms, and comprehensive strategies are needed for broader efficacy. Full article

Background: Treatment with androgen receptor (AR) signaling inhibitors, such as enzalutamide, can induce neural lineage plasticity in prostate cancer, potentially progressing to t-NEPC. However, the molecular mechanisms underlying this enzalutamide-driven plasticity, particularly the contribution of immune signaling pathways, remain poorly understood. Methods: We analyzed transcriptomic profiles of patient samples and prostate cancer cell lines to investigate changes in immune signaling pathways. Interferon gamma (IFNγ), interferon alpha (IFNα), and interleukin 6 (IL6)-Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signaling were assessed in enzalutamide-sensitive and -resistant prostate cancer cells. Functional assays were conducted to examine cell responsiveness to cytokine stimulation and susceptibility to STAT1 inhibition using fludarabine. Results: Immune-related pathways, including IFNγ, IFNα, IL6-JAK-STAT3, and inflammatory responses, were significantly suppressed in NEPC patient samples compared to those with castration-resistant prostate cancer (CRPC). Enzalutamide-resistant and NEPC cells exhibited markedly impaired IFNγ and IL6 signaling. In contrast, early-stage enzalutamide treatment paradoxically enhanced IFNγ and IL6 responsiveness. Transcriptomic profiling revealed coordinated upregulation of E2F target genes and activation of IFNα/IFNγ and JAK/STAT signaling pathways during early treatment. Importantly, these early-stage cells remained highly sensitive to IFNγ and IL6 stimulation and showed increased susceptibility to STAT1 inhibition by fludarabine, a sensitivity that was lost in resistant cells. Conclusions: Early enzalutamide treatment enhances immune responsiveness, while the development of resistance is associated with suppressed immune signaling and increased lineage plasticity. These results suggest a therapeutic window where combining enzalutamide with STAT inhibitors may delay or prevent lineage plasticity and resistance. Full article

Chronic inflammatory disorders of the apocrine gland (CIDAP), such as hidradenitis suppurativa (HS), are characterized by painful, recurrent lesions in apocrine gland-rich areas. First-line treatments—including retinoids and antibiotics—often fail to prevent recurrence and biofilm formation, necessitating the use of targeted biologic therapies. This review evaluated U.S.-based randomized controlled trials and cohort studies published between 2014 and 2024 on the efficacy of such therapies in adult HS patients. A total of 13 studies met inclusion criteria. Agents targeting interleukins (IL-17A, IL-17F, IL-23, IL-1α, IL-36) and TNF-α were assessed, with outcomes including HiSCR, Sartorius scores, DLQI, and patient-reported measures. IL-17 inhibitors (secukinumab, bimekizumab) and IL-1 inhibitors (bermekimab, anakinra) demonstrated promising reductions in inflammatory burden and improved quality of life. TNF-α inhibitors, particularly adalimumab and infliximab, consistently achieved HiSCR and HSS improvements. Guselkumab (IL-23) showed limited efficacy in HiSCR but modest pain relief. Safety profiles were generally acceptable across agents, with few serious adverse events. Limitations across studies included small sample sizes, lack of control arms, and short follow-up durations. These findings underscore the therapeutic potential of biologic agents in managing HS. A greater emphasis on biomarker-guided treatment selection and interdisciplinary collaboration is warranted to optimize long-term outcomes for patients. Full article

The unique ability of oncolytic viruses (OVs) to replicate in and destroy malignant cells while leaving healthy cells intact and activating the host immune response makes them powerful targeted anti-cancer therapeutic agents. Vesicular stomatitis virus (VSV) only causes mild and asymptomatic infection, lacks pre-existing immunity, can be genetically engineered for enhanced efficiency and improved safety, and has a broad cell tropism. VSV can facilitate targeted delivery of immunostimulatory cytokines for an enhanced immune response against cancer cells, thus decreasing the possible toxicity frequently observed as a result of systemic delivery. In this study, the oncolytic potency of the two rVSV versions, rVSV-dM51-GFP, delivering green fluorescent protein (GFP), and rVSV-dM51-mIL12-mGMCSF, delivering mouse interleukin-12 (mIL-12) and granulocyte-macrophage colony-stimulating factor (mGMCSF), was compared on the four murine cancer cell lines of different origin and healthy mesenchymal stem cells (MSCs) at 24 h post-infection by flow cytometry. Lewis lung carcinoma (LL/2) cells were demonstrated to be more susceptible to the lytic effects of both rVSV versions compared to melanoma (B16-F10) cells. Detection of expression levels of antiviral and pro-apoptotic genes in response to the rVSV-dM51-GFP infection by quantitative PCR (qPCR) showed lower levels of IFIT, RIG-I, and N-cadherin and higher levels of IFNβ and p53 in LL/2 cells. Subsequently, C57BL/6 mice, infused subcutaneously with the LL/2 cells, were injected intratumorally with the rVSV-dM51-mIL12-mGMCSF 7 days later to assess the synergistic effect of rVSV and immunostimulatory factors. The in vivo study demonstrated that treatment with two rVSV-dM51-mIL12-mGMCSF doses 3 days apart resulted in a tumor growth inhibition index (TGII) of over 50%. Full article

The spleen is essential for immunity, mediating host defense against pathogens and regulating immunological homeostasis. Western-style diets commonly cause the aggregation of body fat and the emergence of obesity. This state might lead to damage to the spleen’s functions. However, the effects of Western-style diets on gene expression and metabolic regulation in the spleen have not yet been fully explored. In this study, C57BL/6 mice were fed either a high-fat diet (HFD) or standard chow (CHFD) for 10 weeks starting at 8 weeks old. Weekly weights were recorded, and spleens were weighed at 18 weeks. The results showed that HFD mice had significantly higher body weights from 12 weeks (p < 0.05) and a higher splenic index at 18 weeks (p < 0.01). HE staining revealed disrupted spleen structures and infarcted areas in the HFD group. Transcriptome sequencing highlighted immune-related pathways, including inflammatory response and interleukin-6 production. Among the differentially expressed genes (DEGs), PCK1, ALDH9A1, and ALDH7A1 were significantly upregulated in the HFD group, whereas PLA2G2F and PLA2G4F exhibited significant downregulation. APOB emerged as a key hub gene in PPI analysis. Metabolomics analysis identified significantly different metabolites (SDMs), including Rifamycins, 7-Ketodeoxycholic Acid, Folinic Acid, and Lotaustralin, as key biomarkers for an HFD, while 1-Methylnicotinamide and Prostaglandin E1 were significant for CHFD. KEGG enrichment linked glycerophospholipid and arachidonic acid metabolism to both transcriptome and metabolome results. The joint analysis of transcriptome and metabolome data revealed that SLC22A8 was negatively correlated with Biliverdin and 1-methylnicotinamide, and MCPT1 was inversely correlated with 7-Ketodeoxycholic Acid. These findings offer insights into the molecular mechanisms and metabolites that influence spleen immunity and systemic immune homeostasis. Full article

Insulin resistance is a key driver of metabolic disorders, including type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), progressing to non-alcoholic steatohepatitis (NASH). This study investigated the effects of geniposide (GP) on insulin sensitivity and hepatic fibrosis in a high-fat diet (HFD)-induced NASH model. C57BL/6 mice were fed an HFD for five weeks and subsequently divided into normal chow (NC), HFD, HFD with GP 50 mg/kg (GP50), and HFD with GP 100 mg/kg (GP100) groups. The treatments were administered orally for 12 weeks. GP treatment significantly reduced body weight as well as epididymal fat and liver weights, while no differences were observed in food intake. Improvements in glucose and lipid metabolism were observed in oral glucose tolerance tests, homeostatic model assessment of insulin resistance (HOMA-IR), and blood lipid profiles. Histological analyses revealed that GP suppressed adipocyte hypertrophy and hepatic lipid accumulation and hepatic fibrosis. To further elucidate molecular mechanisms of GP, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was conducted in the liver tissue. GP downregulated expression of inflammatory markers, including F4/80, tumor necrosis factor (TNF)-α, and interleukin (IL)-6. GP treatment modulated genes involved in insulin signaling including Janus kinase 2 (JAK2), insulin receptor (INSR), insulin receptor substrate 2 (IRS-2), and protein kinase B (AKT1) gene expression levels. This suggests GP suppresses inflammation and mitigates insulin resistance by activating the INSR–IRS2–Akt pathway. Additionally, GP enhanced adenosine monophosphate-activated protein kinase (AMPK) expression, suggesting its potential role in improving glucose and lipid metabolism. In conclusion, GP improves insulin resistance, inflammation, and hepatic fibrosis, highlighting its therapeutic potential for NASH and related metabolic disorders. Full article

Objectives: Evaluation of the predictive potential of pre-CAR-T [¹⁸F]FDG PET/CT in Diffuse Large B-Cell Lymphoma (DLBCL) patients concerning Cytokine Release Syndrome (CRS) and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS). Methods: Eighteen DLBCL patients (mean age: 60 ± 12 years) who underwent pre-therapeutic [¹⁸F]FDG-PET/CT and CAR-T cell therapy were retrospectively included. Median follow-up time was ten months (IQR6-16) after CAR-T cell infusion. Age, sex, serum lactate dehydrogenase (LDH), interleukin-6 (IL-6), C-reactive protein (CRP), and modified Endothelial Activation and Stress Index (mEASIX) were obtained. Potential occurrence of CRS/ICANS and the SUV_max were evaluated. Pearson and Spearman correlations, group comparisons (Mann–Whitney U-test) and the odds ratio (OR) were calculated. P values below 0.05 were defined as statistically significant and 95%-confidence intervals (CI) were calculated. Results: Pre-therapeutic SUV_max correlated positively with LDH (r = 0.5; p = 0.02), with the grade of CRS (r = 0.5; p = 0.03) and with the grade of ICANS (r = 0.6; p = 0.01). Appearance of ICANS was significantly correlated with pre-therapeutic SUV_max (p = 0.03; U = 7.0; Z = −2.2). Using ROC analysis and Youden’s index, an SUV_max threshold of 17 (AUC: 0.865; p < 0.01) was defined. Patients exceeding a pre-therapeutic SUV_max of 17 had a significantly higher risk of CRS grade > 1 (OR = 22; CI 2, 314; p = 0.03) and ICANS grade > 1 (OR = 18; CI 1, 271; p = 0.04). Conclusions: Pre-therapeutic SUV_max may be a useful marker for identifying DLBCL patients at risk for CRS and ICANS. Full article

Background: Glaesserella parasuis (GPS) is a conditional pathogen that colonizes the upper respiratory tract in pigs and causes Glässer’s disease, resulting in high morbidity and mortality in piglets. GPS infection increases the vascular endothelial permeability, but the mechanism has not been fully elucidated. Luteolin (Lut) is a naturally occurring flavonoid found in plants such as vegetables, herbs, and fruits, but its potential to treat the increased vascular endothelial permeability caused by GPS infection has not been evaluated. Results: This study revealed that GPS infection induces increased vascular endothelial permeability in porcine iliac artery endothelial cells (PIECs) by increasing the gene expressions of tumor necrosis factor (TNF), interleukin 6 (IL-6), IL-8, and IL-1β, and by regulating F-actin cytoskeleton reorganization. Mechanistically, GPS infection or Cluster of differentiation 44 (CD44) overexpression significantly increased the expressions of vascular-endothelial-permeability-related proteins (CD44; vascular endothelial growth factor (VEGFA); matrixmetalloProteinase-3 (MMP-3); MMP-9; and SRC proto-oncogene, non-receptor tyrosine kinase (c-Src)) and increased the vascular endothelial permeability; these changes were alleviated by a Lut treatment or CD44 silencing in the PIECs. Conclusions: This study comprehensively illustrates the potential targets and molecular mechanism of Lut in alleviating the GPS-induced increase in vascular endothelial permeability. The CD44 pathway and Lut may be an effective target and antibiotic alternative, respectively, to prevent the increased vascular endothelial permeability caused by GPS. Full article

Oxidative stress (OS) is a major concern in young poultry and livestock, prompting extensive research on OS models. This study aimed to systematically investigate the dynamic effects and temporal trends of OS induced with lipopolysaccharide (LPS) over time. Twenty-eight piglets were randomly divided into four groups and equally intraperitoneally injected with LPS at doses of 0 μg/kg (control), 50 μg/kg (L-LPS), 100 μg/kg (M-LPS) and 150 μg/kg (H-LPS) body weight, respectively. The results showed that total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and catalase (CAT) were decreased, while malondialdehyde (MDA), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), diamine oxidase (DAO) and D-lactic acid (D-LA) were increased in the M-LPS and H-LPS group on day 1 in comparison with the control group, but no differences were found among treatments on day 7. However, LPS treatments gave rise to varying degrees of pathological injury in the intestines, livers and spleens on day 7. Metabolomics analysis indicated that compared with the control group, glycyl-valine, histamine and lepidine F were decreased in the M-LPS group. Most differentially expressed metabolites were enriched in amino acid-related metabolism pathways on both day 1 and day 7. Microbiome analysis identified that Oscillibacter_sp._CAG:241 was decreased in the M-LPS group compared with the control group on day 1, while Bacteroides_thetaiotaomicron and Lactobacillus_amylovorus were reduced in the M-LPS group on day 7. Collectively, an LPS dose of 100 μg/kg body weight is optimal for inducing acute inflammation in Wuzhishan miniature pigs. These findings highlight the importance of considering both the duration of OS induction and the specific research objectives when establishing OS models. Full article

This pilot study explored whether the ceruloplasmin (CP) and ferritin (FT) levels in ocular fluids could serve as biomarkers for early neurodegenerative diseases (Alzheimer’s, Parkinson’s, and other dementias). CP and FT are known to modulate neurodegenerative tissue responses. We analysed aqueous and vitreous samples from 26 patients (8M/18F, aged 60–85) who were undergoing elective vitreoretinal (VR) surgery. Of these, 14 had idiopathic epiretinal membranes (ERMs), 6 had idiopathic macular holes (MH), and 6 were patients with Alzheimer’s disease (AD) who presented with VR disorders (VRDs). CP, FT, and selected neuroinflammatory mediators such as interferon γ (IFN-γ), interleukin (IL-6), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) were quantified. Odds ratio analysis was applied to assess the CP/FT ratio’s association with subretinal drusen. We found distinct CP and FT profiles in VRD samples. In aqueous fluid, the CP increased and the FT decreased in early-stage ERM, which reduced the CP/FT ratio. Similar patterns were observed in vitreous fluid. The CP levels correlated with the VEGF (aqueous), IL-4 (vitreous), NGF, and BDNF levels; FT correlated with IL-6 and NGF. A higher CP/FT ratio was associated with increased risk for neurodegenerative conditions. Our findings support the quantification of CP and FT in ocular fluids as a promising approach for identifying early neurodegenerative changes and suggest that the CP/FT ratio may be linked to drusen imaging and clinical neurodegenerative history. Full article