Fig 1: Group-wise comparison of z-scores from age- and sex-corrected CSF levels of the 60 kDa brevican fragment (A–C) and the 150 kDa neurocan-C fragment (D–F) as measured via immunoblots (normalized to controls). Cutouts of example western blots of cleaved brevican (A) and neurocan (D) immunoreactivity in individual CSF samples and a reference sample loaded on all gels for calibration. (C) and (F) show the ratios of cleaved brevican (B) and cleaved neurocan (E) to the total immunoreactivity determined for these proteoglycans (CSF cl.BCAN and cl./total BCAN: Ctr. n = 26, ALS n = 14, Epi n = 24, CSVD n = 22; CSF cl. NCAN and CSF cl./total NCAN: Ctr. n = 25, ALS n = 13, Epi n = 24, CSVD n = 20). Statistical significance is indicated (*p = 0.05, **p = 0.005, ***p = 0.0005, ****p < 0.0001). Ctrl, control; ALS, amyotrophic lateral sclerosis; Epi, epilepsy; CSVD, cerebral small vessel disease; HA, hypertensive arteriopathy; CAA, cerebral amyloid angiopathy; BCAN, brevican; NCAN, neurocan; CSF, cerebrospinal fluid; cl., cleaved.
Fig 2: Spearman’s correlation matrix of the concentrations of ECM proteoglycans brevican and neurocan in the CSF and serum of all patients including controls with demographic and serological factors measured during diagnostic work up. Values show the Spearman rank results (significant correlations are indicated in bold). R values are color-coded with blue colors showing positive correlations, red showing negative correlations, and white showing insignificant correlations. BCAN, brevican; NCAN, neurocan; cl., cleaved; QAlb, albumin quotient; IgG index, Immunoglobulin G index.
Fig 3: Group-wise comparison of z-scores from age- and sex-corrected total levels of brevican (A,B) and neurocan (C,D) as measured via ELISAs in CSF (A,C) and serum (B,D) samples (CSF BCAN: Ctr. n = 26, ALS n = 16, Epi n = 25, CSVD n = 22; CSF NCAN: Ctr. n = 26, ALS n = 15, Epi n = 24, CSVD n = 22; Serum BCAN: Ctr. n = 23, ALS n = 10, Epi n = 24, CSVD n = 22; Serum NCAN: Ctr. n = 26, ALS n = 10, Epi n = 26, CSVD n = 22). No statistical significances were detected between groups. (E) The concentrations of total brevican and total neurocan in the CSF correlate with each other (r? = 0.6211, p < 0.0001). CSF, cerebrospinal fluid; Ctrl, control; ALS, amyotrophic lateral sclerosis; Epi, epilepsy; CSVD, cerebral small vessel disease.
Fig 4: Graphical summary of AD-related changes detected in ECM proteins or RNA levels in the hippocampus, frontal, temporal and parietal cortex. Abbreviations: ACAN—aggrecan; BCAN—brevican; HAPLN1—Hyaluronan And Proteoglycan Link Protein 1; NCAN—neurocan; TNR—tenascin-R; cl—cleaved fragment; fl—full length; t—total. Graphical symbols as specified in the box above the figure indicate if findings are based on group-wise comparisons or on correlations with the Braak stages.
Fig 5: Spearman’s correlation matrix of the concentrations of ECM proteoglycans brevican and neurocan in the CSF of all patients including controls with demographic and serological factors measured during diagnostic work up. Values show the Spearman rank results (significant correlations are indicated in bold). R values are color-coded with blue colors showing positive correlations, red showing negative correlations. BCAN, brevican; NCAN, neurocan; cl., cleaved; QAlbumin, albumin quotient; t-Tau, total tau; p-Tau, phosphorylated tau; Aß 1-40, ß-amyloid 1-40; Aß 1-42, ß-amyloid 1-42; Aß Ratio, ß-amyloid(1-42)/(1-40)-ratio; NF-L, neurofilament light chain; IgG index, Immunoglobulin G index; MMSE—mini mental state examination.
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