Additional file 1: of YKL-40 (Chitinase 3-like I) is expressed in a subset of astrocytes in Alzheimer’s disease and other tauopathies

Figure S1. Semi-automated method for pathological burden quantification. For all conditions tau and GFAP were assessed using a randomized computer-based quantification of patterns and severity in immunohistochemical stains. Cortical grey matter of each case was delimited blinded to clinical phenotypes (A). We developed an in-house algorithm that allows defining randomized regions of interest (ROIs) on a full-section scan (B–C), to compute density of protein expression (D) and to quantify the number of pathological objects (E). (TIF 4423 kb

Relationship between age quartiles, Aβ₄₂ and X-tau in 3 cohorts combined.

<p>Scatter plots by age quartiles with the x-axis showing for Aβ₄₂ the combined z scores and raw values by cohort. The y-axis shows the log transformed P-tau181 and T-tau raw scores by cohort and the combined z scores. Individual subjects are shown as circles for NYU, triangles for ADNI and squares for NACC. The outcome groups are indicated by color with the cross-sectional NL in blue, Stable NC in gray, and Future MCI/AD in orange. For each quartile, the linear fit is shown as a solid light blue line and the quadratic fit as a solid red line. The shaded area represents the area outside the 95% CI of the Aβ₄₂ values for each quartile and the vertical dotted line is at the mean Aβ₄₂ for each quartile.</p

Aβ₄₂ in the prediction of X-tau by age quartiles.

<p>Aβ₄₂ in the prediction of X-tau by age quartiles.</p

Subject flow chart.

<p>The patient flow chart shows the inclusion and exclusions of subjects in the analyses conducted for this study.</p

Demographics and baseline descriptive variables for outcome groups.

<p>Demographics and baseline descriptive variables for outcome groups.</p

Percentile rank of the annual percent change in Aβ₄₂ (ε4 genotype and outcome group).

<p>The percentile rankings (by cohort) of the annual percent change in Aβ₄₂ are shown on the y-axis. The subjects are split by E4 carrier status on the x-axis then by Outcome group which is indicated with gray markers for stable NC with baseline Aβ₄₂ levels below the 75^th percentile and light red for those above and black for Future MCI/AD with baseline Aβ₄₂ levels below the 75^th percentile and red for those above. NYU subjects are represented as circles and ADNI as triangles.</p

Cross sectional study demographics and descriptive variables by cohort.

<p>Cross sectional study demographics and descriptive variables by cohort.</p

Relationship of X-tau with Aβ₃₈ and Aβ₄₀.

<p>Scatter plots for n = 233 depicting Aβ₃₈ and Aβ₄₀ on the x-axis and the natural log transformation of X-Tau (and the associated raw values) on the y-axis. The outcome groups are indicated by color with the cross-sectional NL in blue, Stable NC in gray, and Future MCI/AD in orange. The linear fit is shown as a solid light blue line.</p

Linear regression models predicting X-tau (log transformed) by cohort.

<p>Linear regression models predicting X-tau (log transformed) by cohort.</p

Effect of CALHM1 on <b>Aβ</b>_1-42- induced cell toxicity.

<p>HEK-293 cells over-expressing CALHM1-WT, CALHM1-G330D and CALHM1-P86L were treated with 2 μM Aβ_1-42 oligomers for 24h. Cell viability was measured by MTT reduction. Data are the mean ± SEM of three independent experiments performed in triplicate. * <i>P</i><0.05 vs untreated cells by student t test.</p