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O5‐06‐02: Elucidating the gene expression changes that underpin cholinergic dysfunction in a mouse model of Alzheimer's disease
Author(s) -
McKeever Paul M.,
Hesketh Andrew,
Favrin Giorgio,
Oliver Stephen,
St. George-Hyslop Peter,
Robertson Janice
Publication year - 2015
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.2015.07.476
Subject(s) - choline acetyltransferase , cholinergic , cholinergic neuron , forebrain , biology , neuroscience , microbiology and biotechnology , central nervous system
were selected among those exhibiting the strongest variation in terms of fluorescence intensity (the 2.5 % highest and lowest variations). From the selected, enrichment pathway analysis were performed using the Ingenuity database. Results:Data for 18,049 different genes were generated after our different control processes and we finally selected 820 hits showing strong impact on the APP metabolism. Pathway enrichment analysis identified canonical-pathways such as IGF-1 signaling (P1⁄41.1E-05), Cholesterol Biosynthesis (P1⁄41.5E-05) and JAK/ Stat Signaling (P1⁄42.2E05). Among the 150 genes localized in the known susceptibility loci, 7 genes were identified as modulator of APP metabolism. Conclusions: Characterization of these modulators could be useful for our in-depth understanding of the APP metabolism and to characterize the impact of the GWAS-defined genetic risk factors on the AD physiopathology.