Additional file 1 of Neuroinflammatory CSF biomarkers MIF, sTREM1, and sTREM2 show dynamic expression profiles in Alzheimer’s disease
Creators: name: Hok-A-Hin, Yanaika S.
name: del Campo, Marta
name: Boiten, Walter A.
name: Stoops, Erik
name: Vanhooren, Melanie
name: Lemstra, Afina W.
name: van der Flier, Wiesje M.
name: Teunissen, Charlotte E.
Publisher: name: figshare
Year: 2023
Subjects: subject: Biochemistry
subject: Cell Biology
subject: Neuroscience
subject: Immunology
subject: FOS: Clinical medicine
subject: 111714 Mental Health
subject: FOS: Health sciences

description: Additional file 1: Figure S1. MIF, sTREM1, and sTREM2 immunoassays show good analytical performance. The MIF immunoassay showed: parallelism within the acceptable criteria, no hook effect was observed, and linearity % across the dilutions is within the acceptable range. The mean recovery % of samples with low and medium spiked concentrations were not within the acceptable range. The sTREM1 immunoassay showed: parallelism within the acceptable criteria, no hook effect was observed, and linearity % across the dilutions were within the acceptable criteria. The mean recovery % of samples with low and high spiked concentrations were not in the acceptable range. The sTREM2 immunoassay showed: parallelism within the acceptable criteria, no hook effect, linearity % across the dilutions, and mean recovery % of all samples were within the acceptable ranges. Figure S2. MIF and sTREM1 levels are increased in AD in the discovery study. The boxplots represent the protein abundance with the median ± interquartile range observed in our proteomics discovery study. MIF levels were increased in AD and MCI-Aβ+ compared to controls and DLB patients. CSF sTREM1 is increased in AD compared to controls and DLB patients. MIF and sTREM1 measured by proteomics were moderate-strongly associated with protein levels measured by immunoassays. * P &lt; 0.05, ** P &lt; 0.01, *** P &lt; 0.001. Abbreviations: MCI-Aβ+, mild cognitive impairment with amyloid pathology; AD, Alzheimer’s disease; DLB, dementia with Lewy bodies. MIF, macrophage migration inhibitory factor; sTREM1, soluble triggering receptor expressed on myeloid cells 1; sTREM2, soluble triggering receptor expressed on myeloid cells 2; NPX, normalized protein expression. Figure S3. MIF, sTREM1, and sTREM2 levels show a similar trend upon stratification for amyloid status. Raw values are presented and boxplots show the median ± interquartile range. Group differences were calculated based on linear regression analysis including age or sex on log-transformed values. No changes in the inflammatory proteins were observed upon stratifying the MCI and DLB group for amyloid status. Abbreviations: MCI, mild cognitive impairment; AD, Alzheimer’s disease; DLB, dementia with Lewy bodies. MIF, macrophage migration inhibitory factor; sTREM1, soluble triggering receptor expressed on myeloid cells 1; sTREM2, soluble triggering receptor expressed on myeloid cells 2. Figure S4. MIF levels are increased in pTau-positive groups upon A/T status stratification. Raw values are presented and boxplots show the median ± interquartile range. Differences in A/T status were calculated by linear regression analysis or by ANCOVA adjusted for age or sex, when applicable, using Log-transformed values. MIF levels were increased in T+ cases within all clinical groups. No changes in sTREM1 levels were observed while sTREM2 levels were increased in T+ cases compared to T- cases in controls. ** P &lt; 0.01, *** P &lt; 0.001. Abbreviations: MCI, mild cognitive impairment; AD, Alzheimer’s disease; DLB, dementia with Lewy bodies. MIF, macrophage migration inhibitory factor; sTREM1, soluble triggering receptor expressed on myeloid cells 1; sTREM2, soluble triggering receptor expressed on myeloid cells 2. Figure S5. Correlation matrix showing the associations between CSF proteins in the total cohort. The correlation matrix heatmap represents Spearman’s correlation coefficient between inflammatory-related proteins, the classical AD CSF biomarkers and MMSE scores in the total cohort. The blue color depicts a positive correlation coefficient, while red depicts a negative correlation coefficient with significance or the specific correlation coefficient, rho. ** P &lt; 0.01, *** P &lt; 0.001. Abbreviations: MIF, macrophage migration inhibitory factor; sTREM1, soluble triggering receptor expressed on myeloid cells 1; sTREM2, soluble triggering receptor expressed on myeloid cells 2; tTau, total tau; pTau, phosphorylated tau; Aβ42, amyloid-beta 1-42; MMSE, mini-mental state examination. Figure S6. Scatterplot showing the associations of inflammatory proteins with CSF biomarkers and MMSE scores. Correlations between inflammatory-related proteins, the classical AD CSF biomarkers and MMSE scores, stratified by clinical diagnosis. Spearman correlations were performed and the rho numbers are depicted. Abbreviations: MCI, mild cognitive impairment; AD, Alzheimer’s disease; DLB, dementia with Lewy bodies. MIF, macrophage migration inhibitory factor; sTREM1, soluble triggering receptor expressed on myeloid cells 1; tTau, total tau; pTau, phosphorylated tau; Aβ42, amyloid-beta 1-42; MMSE, mini-mental state examination. Table S1. Overview of analytical validation parameters. Table S2. Log-transformed means for adjusted models.