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To evaluate the role of plasma clusterin in Alzheimer's disease (AD).Plasma clusterin is a promising biomarker as various studies have shown it to be associated with AD. But other studies have shown that plasma clusterin levels were not related to Alzheimer's disease or presymptomatic AD. Hence the diagnostic value of plasma clusterin is still not conclusive.Neuropsychological assessment, MRI brain, FDG-PET brain and CSF biomarkers of AD were used for establishing the diagnosis of MCI, AD or Vascular dementia. The CSF control group included patients who were having knee or hip surgery and plasma control group included the spouses of patients.Forty-six patients who gave consent for CSF examination and FDG PET brain were included in the study along with 19 control samples. Alzheimer's group had 34 patients and Vascular group had 12 patients. Both had a significantly lower value of clusterin than the control samples (p

The purpose of the study was to determine serum complement factor H (CFH) levels in patients of age related macular degeneration (AMD) and examine its association with CFH Y402H polymorphism. 115 AMD patients and 61 normal controls were recruited in this study. The single nucleotide polymorphism was assayed by real time PCR and serum CFH levels were measured by ELISA and standardized to total serum protein. Chi-square test was applied to polymorphism analysis while Mann Whitney U-statistic for CFH-levels. Mendelian randomization approach was used for determining causal relationship. The genotype frequency differed between the AMD patients (TT- 18.3%, TC-41.3% and CC-40.4%) and controls (TT-76.3%, TC-13.6%, and CC-10.1%) (p = 0001). The frequency of alleles was also significantly different when AMD (T-39% and C-61%) was compared to controls (T-83% and C-17%) (p = 0.0001). Level of serum CFH was significantly lower in AMD patients as compared to normal controls (p = 0.001). Our data showed that the CFH Y402H polymorphism is a risk factor for AMD in the North Indian population. Mendelian randomization approach revealed that CFH Y402H polymorphism affects AMD risk through the modification of CFH serum levels.

BACKGROUND AND OBJECTIVES: We earlier reported elevated chemokine ligand-2 (CCL2) in Indian amyotrophic lateral sclerosis (ALS) patients. We now analysed chemokine receptor-2 (CCR2), the receptor of CCL2, in these ALS patients. METHODS: Indian sporadic ALS patients (n=50) were included on the basis of El Escorial criteria. Percentage (%) of CCR2 expressing peripheral blood mononuclear cells (PBMCs) was evaluated using Flow Cytometry. Real Time Polymerase Chain Reaction (PCR) was used to quantitate CCR2 mRNA expression in PBMCs. Normal controls (n = 40) were also included for comparison. RESULTS: Flow Cytometry revealed significantly reduced CCR2 expressing PBMCs in the ALS patients. We also found a significant decline in number of CCR2 expressing PBMCs in limb onset ALS when compared to bulbar onset ALS. PBMCs from ALS patients showed substantial down-regulation of CCR2 mRNA. CCR2 mRNA expression was found to be decreased among limb ALS patients as compared to bulbar onset ALS. Further, the count of CCR2+ PBMCs and CCR2 mRNA transcript in PBMCs was significantly lower in severe and moderate ALS as compared to ALS patients with mild impairments. CONCLUSIONS: Downregulation of PBMCs CCR2 may indicate its etio-pathological relevance in ALS pathogenesis. Reduced PBMCs CCR2 may result in decreased infiltration of leukocytes at the site of degeneration as a compensatory response to ALS. CCR2 levels measurements in hematopoietic stem cells and estimation of comparative PBMCs count among ALS, disease controls and normal controls can unveil its direct neuroprotective role. However, the conclusions are restricted by the absence of neurological/non-neurological disease controls in the study.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. We have shown previously that mice deficient in monocyte chemoattractant protein-1 (MCP1/CCL2) or its receptor (CCR2) develop the features of AMD in senescent mice, however, the human genetic evidence so far is contradictory. We hypothesized that any dysfunction in the CCL2 and its receptor result could be the contributing factor in pathogenesis of AMD. METHODS AND FINDINGS: 133 AMD patients and 80 healthy controls were enrolled for this study. Single neucleotid Polymorphism for CCL2 and CCR2 was analyzed by real time PCR. CCL2 levels were determined by enzyme-linked immunosorbent assay (ELISA) after normalization to total serum protein and percentage (%) of CCR2 expressing peripheral blood mononuclear cells (PBMCs) was evaluated using Flow Cytometry. The genotype and allele frequency for both CCL2 and CCR2 was found to be significantly different between AMD and normal controls. The CCL2 ELISA levels were significantly higher in AMD patients and flow Cytometry analysis revealed significantly reduced CCR2 expressing PBMCs in AMD patients as compared to normal controls. CONCLUSIONS: We analyzed the association between single neucleotide polymorphisms (SNPs) of CCL2 (rs4586) and CCR2 (rs1799865) with their respective protein levels. Our results revealed that individuals possessing both SNPs are at a higher risk of development of AMD.