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Additional file 6: Table S5. Description of the participants in EMIF-AD MBD cohort.

Additional file 4: Fig. S1. Comparison of the CSF proteomes of the two App knock-in models reveals alterations in ECM proteins. a Volcano plots displaying the changes in protein levels in CSF from AppNL-F/NL-F vs AppNL-G-F/NL-G-F mice. Dash line: p = 0.05. b Heatmap of significantly (p < 0.05) altered proteins in AppNL-F/NL-F mice as compared to AppNL-G-F/NL-G-F mice. Proteins were sorted into upregulated and downregulated proteins in the AppNL-G-F/NL-G-F mice and by significance from highest to lowest (top to bottom).

Additional file 11: Fig. S4. CSF-decorin levels correlates with Aβ pathology in the brains of AppNL-F/NL-F mice. a Spearman’s correlation analysis of parameters related to Aβ plaque load and decorin levels between 12 months old AppNL-F/NL-F and Appwt/wt mice, b AppNL-G-F/NL-G-F and Appwt/wt mice. The corresponding figures for each parameter are denoted. The correlation coefficients are displayed (*p < 0.05, **p < 0.01, ***p < 0.001). The red color represents positive correlation, and the green color represents negative correlation according to the scale bars in the right column.

Additional file 3: Table S3. Significantly altered ECM associated proteins in mouse CSF identified by MS and PEA.

Additional file 9: Fig. S2. CSF-decorin negatively correlates with CSF-t-tau and CSF-p-tau in the whole EMIF-AD MBD cohort. a Correlations of CSF-DCN and CSF-Aβ42, b CSF-DCN and CSF-t-tau, c CSF-DCN and CSF-p-tau in the whole EMIF-AD MBD cohort (n = 310), including NC (n = 139), MCI (n = 92) and AD (n = 79) were analyzed. The regression coefficients (Beta) and p-values are displayed. DCN decorin.

Neuronal ischemia results in chloride gradient alterations which impact the excitatory&ndash, inhibitory balance, volume regulation, and neuronal survival. Thus, the Na+/K+/Cl&minus, co-transporter (NKCC1), the K+/ Cl&minus, co-transporter (KCC2), and the gamma-aminobutyric acid A (GABAA) receptor may represent therapeutic targets in stroke, but a time-dependent effect on neuronal viability could influence the outcome. We, therefore, successively blocked NKCC1, KCC2, and GABAA (with bumetanide, DIOA, and gabazine, respectively) or activated GABAA (with isoguvacine) either during or after oxygen-glucose deprivation (OGD). Primary hippocampal cultures were exposed to a 2-h OGD or sham normoxia treatment, and viability was determined using the resazurin assay. Neuronal viability was significantly reduced after OGD, and was further decreased by DIOA treatment applied during OGD (p &lt, 0.01) and by gabazine applied after OGD (p &lt, 0.05). Bumetanide treatment during OGD increased viability (p &lt, 0.05), while isoguvacine applied either during or after OGD did not influence viability. Our data suggests that NKCC1 and KCC2 function has an important impact on neuronal viability during the acute ischemic episode, while the GABAA receptor plays a role during the subsequent recovery period. These findings suggest that pharmacological modulation of transmembrane chloride transport could be a promising approach during stroke and highlight the importance of the timing of treatment application in relation to ischemia-reoxygenation.