Fig. 7

Validation of Cotl1 as a novel microglia-specific protein with pathophysiological significance in human AD. a Comparison of Cotl1 transcript and protein expression in CNS cells (astrocytes, microglia, neurons and oligodendrocytes). Data were derived from existing brain cell-type specific RNA sequencing and proteomics datasets [8, 29]. b Cotl1 protein expression in post-mortem human brain (frontal cortex) comparing non-disease controls, pathologically confirmed AD, clinically confirmed cases of Parkinson’s disease (PD) and patients with both AD and PD (n = 10 individuals per group). ANOVA and post-hoc pairwise t-test p-values are shown. Protein-level expression data from human post-mortem brains was obtained from a published proteomic dataset [18]. c Correlation between Cotl1 protein expression in post-mortem human brain with neurofibrillary tangle neuro-pathological grade (BRAAK stage). Correlation coefficient (R) and significance of the association are shown. d Cotl1 was identified as a member of a glial-enriched protein module identified by weighted co-expression network analysis of human post-mortem brain proteomic data from 40 cases (10 controls, 10 AD, 10 PD and 10 AD+PD) [18]. Human AD risk genes identified by MAGMA analysis of AD genome wide association studies (iGAP study) in this module are indicated (light blue). e Immufluorescence micrographs from post-mortem human brain (frontal cortex) showing microglial marker CD68 (Red) and Cotl1 expression (Green). Co-localization between CD68 and Cotl1 is shown in the merged channel below. f Immunofluorescence micrographs from post-mortem human brain (Frontal cortex) showing astrocytic Gfap (Red) and Cotl1 (Green) expression (nuclei in Blue: DAPI). Lack of co-localization between Gfap and Cotl1 is shown in the merged channel. g Immunohistochemistry micrographs from AD and non-disease control post-mortem human brains (frontal cortex) showing increased microglial Cotl1 expression (Brown) in AD as compared to non-disease controls (representative images from n = 4 AD and n = 4 non-AD cases). Quantitative analysis of Cotl1 immunoreactivity is shown (right)