Additional file 1: of Cerebrospinal fluid soluble TREM2 in aging and Alzheimer’s disease

Figure S1 showing ELISA validation; Figure S2 showing freeze–thaw cycles; Figure S3 showing PET imaging versus CSF Aβ42 in patients; Figure S4 showing a scatter plot of CSF sTREM2 in relation to CSF levels of Aβ38 MSD (A), Aβ40 MSD (B) and Aβ42 MSD (C) in the Norwegian AD/MCI/control cohort; Figure S5 showing a scatter plot of different CSF Aβ measures with Innotest® and MSD; Figure S6 showing a scatter plot of CSF sTREM2 in relation to levels of Aβ42 (A), T-tau (B) and P-tau (C) in CSF in the Swedish AD/control cohort; Figure S7 showing a surface plot of CSF sTREM2 in relation to age and Aβ38 MSD (A) and in relation to age and Aβ40 MSD (B) in controls; Table S1 presenting correlations between different CSF Aβ measures (Aβ42 Innotest®, Aβ38 MSD, Aβ40 MSD and Aβ42 MSD); and Table S2 presenting correlation analyses between different CSF sTREM2 and age and biomarkers (Aβ42 Innotest®, Aβ38 MSD, Aβ40 MSD and Aβ42 MSD, T-tau and P-tau). (PDF 647 kb

List of SNPs with observed association p-value being less than 1.00E-05.

<p>Chromosomal position is specified in Build 36 (hg18). OR refers to odds ratio and 95%CI refers to 95% confidence interval. <i>TRIM36</i> refers to tripartite motif containing 36 gene. <i>ZBTB16</i> refers to zinc finger and BTB domain containing 16 gene.</p><p>List of SNPs with observed association p-value being less than 1.00E-05.</p

Manhattan plot.

<p>Red line represents genome-wide significance threshold of 5.00E-08, while the blue line corresponds to the suggestive threshold of p = 1.00E-05.</p

QQ plot.

<p>This figure represents the distribution of p-values observed in the presented genome-wide association study of ADHD. The shaded area represents the 95% confidence interval.</p

Results of protein-protein link evaluation in DAPPLE. List of indirect interactors.

<p>Presented p-values reflect the probability that by chance individual interactors would be as connected to seed proteins (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122501#pone.0122501.s002" target="_blank">S2 Table</a>) as was observed in the constructed network.</p><p>Results of protein-protein link evaluation in DAPPLE. List of indirect interactors.</p

Protein-protein interaction network build from proteins encoded in associated intervals.

<p>The colored, full circles represent proteins encoded in associated intervals (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122501#pone.0122501.s002" target="_blank">S2 Table</a>). The smaller, grey circles represent interactors of indirect connections. Functionally, the DAPPLE-constructed diagram can be divided into two main groups: group “A” mostly involved in the regulation of gene expression and inflammation; and group “B” mostly involved in cell adhesion.</p

Summary of most frequently reported adverse events.

<p>SD = single dose; RD = repeat dose.</p><p>²Amyloid-related imaging abnormality-hemorrhage (ARIA-H)</p><p>¹Amyloid-related imaging abnormality-edema (ARIA-E);</p><p>Summary of most frequently reported adverse events.</p

Summary of patients’ baseline characteristics.

<p>SD = single dose; RD = repeat dose; SE = standard error.</p><p>³Three patients participated in two dose levels of the single dose study and therefore the PGx sample was collected at the first dosing level in which they participated and not the second dosing level. <i>APOE</i> ε4 overall carriage frequency was calculated using the PGx population (n = 15), i.e., patients who participated in more than one dosing level were only taken into account once.</p><p>²Six patients participated in part A and re-entered part B. Therefore the pharmacogenetic (PGx) sample was collected when the patients participated in part A and no PGx sample was collected during part B. <i>APOE</i> ε4 overall carriage frequency was calculated using the PGx population (n = 44), i.e., patients who participated in both parts were only taken into account once.</p><p>¹Values ranged from 20 to 26 for all patients except one, who scored 28.</p><p>Summary of patients’ baseline characteristics.</p

GSK933776 plasma pharmacodynamics.

<p>A) Geometric mean plasma Aβ concentration–time plots over the three dosing intervals (semi-log plot). Plasma levels of total Aβ42 and Aβ increased whereas plasma levels of free Aβ decreased in dose-dependent manner. Peak:trough ratios for Aβ decreased with increasing dose of GSK933776. B) Week 12 ratio to baseline for CSF Aβ (Aβ1–42 and AβX–42) concentrations. Presented as individual values and mean (95%CI). There were no significant changes from baseline for Aβ1–42 or AβX–42.</p

GSK933776 plasma pharmacokinetics.

<p>Time-course of plasma concentrations of GSK933776 by dose: medians (lines) and individual data (dots). LLQ is 100 ng/mL for the 0.1 mg/kg dose and 5 μg/mL for the 1, 3, and 6 mg/kg doses. SD = single dose; RD = repeat dose. Maximum plasma concentrations increased with dose.</p