RUB » Bibliotheksportal

Lisa Schrewe, Anke Salmen, Denis A. Akkad, Sabine Hoffjan, S. Demir, A. Böhme, Ralf Gold, Andrew Chan

• \(\textbf {Background:}\) Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) \(\textit {in vitro}\), its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of \(\it apoE\) on disease course of EAE and MS. \(\textbf {Methods:}\) \(MOG_{35-55}\) induced EAE in female and male \(\it apoE\)-deficient mice was assessed clinically and histopathologically. \(\it apoE\) expression was investigated by qPCR. The association of the MS severity score (MSSS) and \(\it APOE\) rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. \(\textbf {Results:}\) EAE disease course was slightly attenuated in male \(\it apoE\)-deficient \(\it (apoE^{-/-})\) mice compared to wildtype mice (cumulative median score: \(\it apoE^{-/-}\) = 2 [IQR 0.0–4.5]; wildtype = 4 [IQR 1.0–5.0]; \(\it n\) = 10 each group, \(\it p\) = 0.0002). In contrast, EAE was more severe in female \(\it apoE^{-/-}\) mice compared to wildtype mice (cumulative median score: \(\it apoE^{-/-}\) = 3 [IQR 2.0–4.5]; wildtype = 3 [IQR 0.0–4.0]; \(\it n\) = 10, \(\it p\)= 0.003). In wildtype animals, \(\it apoE\) expression during the chronic EAE phase was increased in both females and males (in comparison to naïve animals; \(\it p\)< 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. \(\textbf {Conclusions:}\) \(\it apoE\) exerts moderate sex-specific effects on EAE severity. However, the results in the \(\it apoE\) knock-out model are not comparable to effects of polymorphic variants in the human \(\it APOE\) gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease.