Premium
P3‐107: Alterations in DNA Methylation Contribute to Neuroinflammation in Alzheimer’s Disease
Author(s) -
Wiswell Roxana,
Guerrero-Preston Rafael,
Cronin Peter,
Mott Jennifer,
Desplats Paula
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1765
Subject(s) - neuroinflammation , dna methylation , epigenetics , methylation , dementia , biology , differentially methylated regions , epigenomics , alzheimer's disease , inflammation , disease , bioinformatics , genetics , medicine , gene , gene expression , immunology
ARG1, CD206, CD86, TREM2, CD163, CHI3L1) and pre(synaptophysin) and post-synaptic (PSD95) markers were measured by RT-PCR and ELISA, respectively. Results: In AD, relative to controls, there was a significant increase in levels of Ab (p<0.001), pTau (p<0.001), CHI3L1 (p1⁄40.015) and microglial markers related to phagocytosis (CD68, p1⁄40.037), antigen presentation (HLA-DR, p1⁄40.044) and immune response (FcgRI, p1⁄40.002). We also observed a significant association between FcgRIIa and FcgRIII and CHI3L1 and FcgRIII in AD (ADand AD+); and between FcgRI and FcgRIII in ASI cohorts (Ctrl+ and AD+). We showed that ASI significantly decreases the expression of FcgRIII (p1⁄40.03) and elevates the expression of anti-inflammatory genes IL4R (p1⁄40.04) and CHI3L1 (p1⁄40.012) in AD cases (AD+ vs. AD-). ASI did not affect Ab, pTau or synaptic proteins. Conclusions: Our findings confirm our previous observations as well as genetic studies that indicate a role for microglia in AD. Interestingly, ASI appears to promote immunosuppression without affecting AD pathology or synaptic proteins. This may be driven at least in part through communication between microglial cells via the FcgR, key receptors involved in the peripheral immune response.