Systematic review and meta-analysis of human transcriptomics reveals neuroinflammation, deficient energy metabolism, and proteostasis failure across neurodegeneration.

Neurobiology of Disease
Ayush NooriSudeshna Das

Abstract

Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) spectrum are defined by the accumulation of specific misfolded protein aggregates. However, the mechanisms by which each proteinopathy leads to neurodegeneration remain elusive. We hypothesized that there is a common "pan-neurodegenerative" gene expression signature driving pathophysiology across these clinically and pathologically diverse proteinopathies. To test this hypothesis, we performed a systematic review of human CNS transcriptomics datasets from AD, LBD, and ALS-FTD patients and age-matched controls in the Gene Expression Omnibus (GEO) and ArrayExpress databases, followed by consistent processing of each dataset, meta-analysis, pathway enrichment, and overlap analyses. After applying pre-specified eligibility criteria and stringent data pre-processing, a total of 2600 samples from 26 AD, 21 LBD, and 13 ALS-FTD datasets were included in the meta-analysis. The pan-neurodegenerative gene signature is characterized by an upregulation of innate immunity, cytoskeleton, and transcription and RNA processing genes, and a downregulation of the mitochondrial electron ...Continue Reading

References

Nov 8, 1986·Lancet·J P BrionP Dustin
May 16, 1984·Biochemical and Biophysical Research Communications·G G Glenner, C W Wong
Aug 28, 1997·Nature·M G SpillantiniM Goedert
Sep 27, 2005·Neurobiology of Disease·Alexander GerhardDavid J Brooks
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Dec 7, 2006·Nucleic Acids Research·Donna MaglottTatiana Tatusova
Jul 24, 2007·Bioinformatics·Aravind SubramanianJill P Mesirov
Oct 3, 2007·PLoS Genetics·Jeffrey T Leek, John D Storey
Dec 25, 2008·Bioinformatics·Audrey KauffmannWolfgang Huber
Mar 23, 2010·Nature Neuroscience·Martin FuhrmannJochen Herms
Aug 7, 2010·Bioinformatics·Benilton S Carvalho, Rafael A Irizarry
Oct 12, 2010·Science Translational Medicine·Bin ZhengGlobal PD Gene Expression (GPEX) Consortium
May 7, 2011·Bioinformatics·Arthur LiberzonJill P Mesirov
Aug 4, 2011·Brain : a Journal of Neurology·Katya RascovskyBruce L Miller
Jun 12, 2013·Cell·Carlos López-OtínGuido Kroemer
Sep 5, 2014·Acta Neuropathologica Communications·Matthew D LiPurvesh Khatri
Sep 23, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Zhen FanPaul Edison
Dec 9, 2014·Nature Communications·David VilchezAndrew Dillin
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Apr 14, 2016·Proceedings of the National Academy of Sciences of the United States of America·Prajwal CiryamMichele Vendruscolo
Sep 24, 2016·Cell·Agnes Toth-PetroczyDebora S Marks
Feb 25, 2017·Cell·Dirk M WaltherF Ulrich Hartl
May 20, 2017·Science·Avinash PatelAnthony A Hyman
Jan 30, 2018·Frontiers in Molecular Neuroscience·Adam LabadorfRichard H Myers
Aug 22, 2018·Lancet Neurology·Aurora ScrivoAna Maria Cuervo
Mar 26, 2019·Journal of Alzheimer's Disease : JAD·Hamel PatelStephen J Newhouse
May 3, 2019·Nature·Hansruedi MathysLi-Huei Tsai
Mar 7, 2020·Science·Evelina SjöstedtJan Mulder

Related Concepts

Alzheimer's Disease
Amyotrophic Lateral Sclerosis
Brain
Cytoskeleton
Down-Regulation
Energy Metabolism
Gene Expression
Genes
Inflammation
Mitochondria

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