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O2‐02‐01: HIGH RESOLUTION STRUCTURE OF AMYLOID‐β(1‐42) FIBRILS
Author(s) -
Willbold Dieter,
Gremer Lothar,
Schölzel Daniel,
Schenk Carla,
Wolfgang Hoyer,
Heise Henrike,
Schröder Gunnar
Publication year - 2018
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.2018.06.2645
Subject(s) - fibril , crystallography , dimer , chemistry , biophysics , protein subunit , protein structure , cryo electron microscopy , amyloid (mycology) , resolution (logic) , biochemistry , biology , inorganic chemistry , organic chemistry , artificial intelligence , gene , computer science
Our goal was to test whether RNA editing in blood reflects the immune regulatory changes that occur in AD. Methods:Whole transcriptome RNA sequencing was performed on peripheral blood specimens from 216 AD cases (105 AA, 111 NHW) and 212 matched controls (105 AA, 107 NHW). REDItools software was used to identify candidate editing events, and the output was filtered for quality. Differentially edited genes were analyzed against the set of genes that are expressed in blood for Gene Ontology term enrichment. Differentially edited sites affecting miRNA binding sites were identified using TargetScan. Results:Editing events were detected at a total of 44985 positions. 449 positions in 254 genes were differentially edited in AA, and 723 positions in 351 genes were differentially edited in NHW. In both AA and NHW, genes with differential editing were enriched for biological processes related to immune regulation (p 1⁄4 0.10), inflammation (p 1⁄4 0.19), and endocytosis (p 1⁄4 0.0010). Nearly half of all differentially edited genes in AA and NHW were associated with either immune system process or vesicle-mediated transport terms. Regulation of amyloid precursor protein catabolism was enriched in NHW. Differentially edited sites affected miRNA binding sites in multiple genes including PAFAH1B2 and HNRNPA1, which have previously been linked to AD-phenotypes in molecular studies. Conclusions: AD cases of both NHW and AA ethnicities have altered RNA editing in genes enriched for biological processes including immune regulation, inflammation, and endocytosis, processes that have previously been implicated in AD pathology. This may be evidence of a post-transcriptional program contributing to the underlying complexity of AD pathophysiology.