Fig 2: Prognostic power of ApoE in stage II CRC cohort and liver metastatic CRC cohort. Kaplan–Meier analyses of overall survival and progression free survival in patients with CRC based on the expression of ApoE. OS and PFS according to ApoE expression in stage II CRC (A,B) and liver metastatic CRC (C,D). The relationship between ApoE expression and PFS benefit from adjuvant chemotherapy in patients with stage II CRC. Treatment with 5-FU based chemotherapy was not associated with a higher rate of PFS both in the ApoE high group (E) and the ApoE low group (F).

Fig 3: Intracranial cerebrospinal fluid (CSF) after severe traumatic brain injury contains EVs, lipoproteins, and albumin. CSF samples from three patients (Pt) collected during the first three days (d) after severe traumatic brain injury were pooled in equal volumes to make a CSF sample (CSF-pool) for size exclusion chromatography (SEC). Individual CSF samples and the CSF-pool were separated by electrophoresis and analysed by immunoblot with antibodies against albumin, apolipoprotein (Apo) E and AI, and EV proteins CD81 and CD9. Sizes of detected proteins are indicated in kilodaltons.

Fig 4: ApoE is increased in microglia in chronic phases of neuropathic pain.a UMAPS of Apoe in different conditions in male mice. Color codes for Apoe log-normalized counts. Tables show fold change (LogFC) and rank of Apoe mRNA in the list of DEGs in males (b) and females (c). Cluster markers were identified using the FindallMakers function in Seurat (two-sided Wilcoxon rank-sum test with Bonferroni correction. Differentially expressed genes between groups were calculated using the Wilcoxon rank-sum test (two-sided) with Bonferroni correction. d Low magnification (top left) and high magnification images of the marked area showing immunostaining against Iba1, GFAP, ApoE, and NeuN in the mouse dorsal horn spinal cord section at day 14 post-SNI. Scale bar is 100 μm for low magnification and 10 μm for high magnification images. e Representative Airyscan images of Iba1, ApoE, and DAPI in the mouse dorsal horn, showing cytoplasmatic expression of ApoE. Scale bar is 10 μm for low magnification and 5 μm for high magnification images. f Representative images of immunostaining for ApoE and Iba1 in the spinal cord of male mice after SNI at day 3, day 14 and 5 months. Bottom images are magnification of area marked in corresponding upper images. Scale bar is 20 μm for low magnification and 10 μm for high magnification images. Similar results were obtained in two independent experiments. g Quantification of ApoE immunostaining signal in microglia in males and females (n = 3 males and three females per condition). ApoE was increased at day 14 and 5 months post-SNI as compared to corresponding sham groups (Day 3, sham versus SNI, q(35) = 0.917, p = 0.99; Day 14, sham versus SNI, q(35) = 11.93, p < 0.0001; 5 Months, sham versus SNI, q(35) = 20.58, p < 0.0001. Data are plotted as mean ± s.e.m., one-way ANOVA followed by Tukey’s multiple comparisons post hoc test. ****p < 0.0001; ns, not significant.

Fig 5: Validation of APOE as a factor in anti-IAV infection.(A and B) Huh7 WT and APOE KO cells were infected with PR8 at an MOI of 0.3. NP+ and M2+ cells were assessed by flow cytometry (A) or immunofluorescence microscopy (B) 12 hours after infection (left), and relative fold infection from three independent experiments with SD was statistically analyzed (right). Scale bars, 100 μm. (C) Huh7 WT and APOE KO cells were infected as in (A), and NP and HA expression was assessed by Western blot. The data shown are representative of three independent experiments. (D and E) Supernatant from the Huh7 WT and APOE KO cells infected as in (A) was collected, the v-RNA was quantified by qRT-PCR (D), and virus titer was detected by plaque assay (E). Data are shown as means ± SD from at least three independent experiments. (F) WT and APOE KD/KO Huh7 cells were infected with PR8 with a low MOI of 0.01, and supernatant was collected to detect the PR8 growth kinetics by plaque assay. The data shown are representative of at least three independent experiments. P values were determined using Student’s t test. *P < 0.05, **P < 0.01, and ***P < 0.001.