The Correlation of Tau Levels with Blood Monocyte Count in Patients with Alzheimer’s Disease

Background: Recent studies have shown that monocytes can phagocytize the tau protein, which may ameliorate tau-type pathology in Alzheimer’s disease (AD). However, there are few clinical studies on the relationship between monocytes and tau-type pathology in AD patients. Objective: We aimed to explore changes in peripheral monocytes and their association with tau protein in AD patients. Methods: A total of 127 clinically diagnosed AD patients and 100 age- and sex-matched cognitively normal controls were recruited for analysis of the correlation of plasma tau levels with the blood monocyte count. Cerebrospinal fluid (CSF) samples from 46 AD patients and 88 controls were further collected to analyze the correlation of CSF tau and amyloid-β (Aβ) levels with the blood monocyte count. 105 clinically diagnosed mild cognitive impairment (MCI) patients and 149 age- and sex-matched cognitively normal controls were recruited from another cohort for verification. Results: Compared to normal controls, AD patients showed a significant reduction in the blood monocyte count. In addition, the monocyte count of AD patients was negatively correlated with CSF t-tau and p-tau levels but not with plasma tau levels. In normal people, monocyte count lack correlation with tau levels both in plasma and CSF. Monocyte count were not correlated with CSF Aβ levels in either group but were negatively correlated with CSF tau/Aβ 42 levels in the AD group. We had further verified the correlations of monocyte count with CSF tau levels in another cohort. Conclusion: This study suggests that monocytes may play an important role in the clearance of tau protein in the brain.

Peripheral Blood Monocyte Abundance Predicts Outcomes in Breast Cancer Patients

Biomarkers of response are needed in breast cancer to stratify patients to appropriate therapies and avoid unnecessary toxicity. Peripheral blood gene expression and cell type abundance were used to identify biomarkers of response and recurrence in neoadjuvant chemotherapy treated breast cancer patients. Higher peripheral blood monocyte abundance after neoadjuvant chemotherapy was associated with improved prognosis in multiple independent cohorts of breast cancer patients.

Propofol Improves Survival In A Murine Model of Sepsis Via Inhibiting Rab5a -Mediated Intracellular Trafficking of TLR4

Background：Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 are still unclear. In view of its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol.Methods: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide or cecal ligation and puncture in vitro and in vivo, and in peripheral blood monocyte from sepsis patients and healthy volunteers. Results: We showed that propofol reduced membrane TLR4 expression on macrophage in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocyte of septic patients, accompanied by increased TLR4 expression on the cell surface. Both were correlated with SOFA score of sepsis patients and higher expression of Rab5a were found in septic non-survivors. Propofol downregulated the expression of Rab5a and TLR4 in these cells.Conclusions：We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Deficits in Monocyte Function in Age Related Macular Degeneration: A Novel Systemic Change Associated With the Disease

Age-related macular degeneration (AMD) is characterized by the accumulation of debris in the posterior eye. In this study we evaluated peripheral blood monocyte phagocytic function at various stages of AMD and in aged matched control participants. Real-time tri-color flow cytometry was used to quantify phagocytic function of peripheral blood monocyte subsets (non-classic, intermediate and classic) isolated from subjects with intermediate or late AMD and compared with age matched healthy controls. Assessment of phagocytic function of monocytes isolated from those with and without reticular pseudodrusen was also made, and the effect of glatiramer acetate on phagocytic function assessed. Phagocytic function was reduced in all subjects with AMD, irrespective of stage of disease. However, there was no correlation between phagocytic function and drusen load, nor any difference between the level of phagocytosis in those with or without reticular pseudodrusen. Treatment with glatiramer acetate increased phagocytosis of classical and non-classical monocytes, normalizing the reduction in phagocytosis observed in those with AMD. These findings suggest that defective systemic phagocytosis is associated with both intermediate and late stages of AMD, highlighting a potential role in the accumulation of debris that occurs early in the disease process. Assessing peripheral monocyte phagocytic function provides further insights into the etiology of this disease and offer a novel therapeutic target.