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P1‐123: Differential Expression in Hippocampus of Alzheimer's Disease Patients
Author(s) -
Rooij Jeroen G.J.,
Meeter Lieke H.H.,
Melhem Shami,
Nijholt Diana,
Rozemuller Annemieke,
Uitterlinden Andre G.,
Meurs Joyce,
Van Swieten John C.
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.2016.06.871
Subject(s) - biology , transcriptome , kegg , gene , hippocampus , gene expression profiling , actin cytoskeleton , genetics , gene expression , neuroscience , cytoskeleton , cell
Background: Alzheimer’s Disease (AD) is the most common form of dementia, affecting approximately 40 million individuals worldwide. One of the most severely affected brain regions is the hippocampus. Despite extensive research, much is still unknown about the exact molecular and genetic mechanisms underlying AD. Genome-wide transcriptomic could provide more insight into AD disease mechanisms. In this study, we are investigating transcriptomic differences in the hippocampus of AD cases and controls. Methods: Isolated RNA from hippocampus tissue of 2 cases and 2 controls was 2x50bp paired-end sequenced on an Illumina HiSeq2000. Adaptors and low-quality bases were trimmed using trim-o-matic, followed by alignment to hg19 using STAR, processing by picard and gene quantification using featurecounts. Pathway and Gene Ontology term enrichments were performed using webgestalt. Results:On average 56,000,000 reads were sequenced per sample. 12,742 protein-coding genes were detected using an average FPKM of > 1. No genes reached transcriptome-wide significance. We selected 324 protein-coding genes with p-value < 0.005 for enrichment analysis. Significantly enriched KEGG pathways were “Calcium Signaling Pathway”, “Long Term Potentiation”, “Alzheimer’s Disease”, “Oocyte Meiosis” and “Regulation of Actin Cytoskeleton”. Significantly enriched GO terms were, amongst others, “Neuron Projection Development”, “Synaptic Vesicle Transport”, “Axon Part” and “Synaptic Vesicle Membrane”. Conclusions: Our preliminary results show enrichment of known brainand neuron-specific pathways and GO-terms amongst the genes differentially expressed upon AD. We will expand our sample set with RNA-Seq and DNA-Methylation arrays to a total of 10 controls and 20 cases (10 ApoE4 carriers and 10 non-carriers). Together, these results will provide more insight into the interplay between known ADand brainspecific genes, as well as identify novel players in these pathways. Data on all 30 samples will be available and presented on the AAIC.