{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:30:32Z","timestamp":1789471832321,"version":"build-2803163510"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The growing prevalence of Alzheimer's disease (AD) is becoming a global health challenge without effective treatments. Defective mitochondrial function and mitophagy have recently been suggested as etiological factors in AD, in association with abnormalities in components of the autophagic machinery like lysosomes and phagosomes. Several large transcriptomic studies have been performed on different brain regions from AD and healthy patients, and their data represent a vast source of important information that can be utilized to understand this condition. However, large integration analyses of these publicly available data, such as AD RNA-Seq data, are still missing. In addition, large-scale focused analysis on mitophagy, which seems to be relevant for the aetiology of the disease, has not yet been performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, publicly available raw RNA-Seq data generated from healthy control and sporadic AD post-mortem human samples of the brain frontal lobe were collected and integrated. Sex-specific differential expression analysis was performed on the combined data set after batch effect correction. From the resulting set of differentially expressed genes, candidate mitophagy-related genes were identified based on their known functional roles in mitophagy, the lysosome, or the phagosome, followed by Protein-Protein Interaction (PPI) and microRNA-mRNA network analysis. The expression changes of candidate genes were further validated in human skin fibroblast and induced pluripotent stem cells (iPSCs)-derived cortical neurons from AD patients and matching healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From a large dataset (AD: 589; control: 246) based on three different datasets (i.e., ROSMAP, MSBB, &amp;amp; GSE110731), we identified 299 candidate mitophagy-related differentially expressed genes (DEG) in sporadic AD patients (male: 195, female: 188). Among these, the AAA ATPase VCP, the GTPase ARF1, the autophagic vesicle forming protein GABARAPL1 and the cytoskeleton protein actin beta ACTB were selected based on network degrees and existing literature. Changes in their expression were further validated in AD-relevant human <jats:italic>in vitro<\/jats:italic> models, which confirmed their down-regulation in AD conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Through the joint analysis of multiple publicly available data sets, we identify four differentially expressed key mitophagy-related genes potentially relevant for the pathogenesis of sporadic AD. Changes in expression of these four genes were validated using two AD-relevant human <jats:italic>in vitro<\/jats:italic> models, primary human fibroblasts and iPSC-derived neurons. Our results provide foundation for further investigation of these genes as potential biomarkers or disease-modifying pharmacological targets.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2023.1101216","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T05:04:54Z","timestamp":1686287094000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Pooled analysis of frontal lobe transcriptomic data identifies key mitophagy gene changes in Alzheimer's disease brain"],"prefix":"10.3389","volume":"15","author":[{"given":"Taoyu","family":"Mei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ordu\u00f1a Dolado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiquan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Berliocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lene Juel","family":"Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2659","DOI":"10.15252\/embj.201489039","article-title":"The small GTP ase Arf1 modulates mitochondrial morphology and function","volume":"33","author":"Ackema","year":"2014","journal-title":"EMBO J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"160089","DOI":"10.1038\/sdata.2016.89","article-title":"Human whole genome genotype and transcriptome data for Alzheimer's and other neurodegenerative diseases","volume":"3","author":"Allen","year":"2016","journal-title":"Sci. Data"},{"key":"B3","first-page":"1134","article-title":"\u00dcber einen eigenartigen schweren Erkrankungsproze\u03b2 der Hirnrincle","volume":"25","author":"Alzheimer","year":"1906","journal-title":"Neurol. Central"},{"key":"B4","doi-asserted-by":"publisher","first-page":"118020","DOI":"10.1016\/j.lfs.2020.118020","article-title":"The role of CREB and BDNF in neurobiology and treatment of Alzheimer's disease","volume":"257","author":"Amidfar","year":"2020","journal-title":"Life Sci"},{"key":"B5","doi-asserted-by":"publisher","first-page":"4282","DOI":"10.1038\/npre.2010.4282.2","article-title":"Differential expression analysis for sequence count data","volume":"12","author":"Anders","year":"2010","journal-title":"Nat. Prec"},{"key":"B6","doi-asserted-by":"publisher","first-page":"101055","DOI":"10.1016\/j.molmet.2020.101055","article-title":"Aster-B coordinates with Arf1 to regulate mitochondrial cholesterol transport","volume":"42","author":"Andersen","year":"2020","journal-title":"Molec. Metab"},{"key":"B7","unstructured":"AndrewsS.\n          FastQC: A Quality Control Tool for High Throughput Sequence Data2010"},{"key":"B8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: Tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3389\/fcell.2020.00239","article-title":"MitophAging: Mitophagy in Aging and Disease","volume":"8","author":"Bakula","year":"2020","journal-title":"Front. Cell Dev. Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1002\/cm.20388","article-title":"Cytoskeletal pathologies of Alzheimer disease","volume":"66","author":"Bamburg","year":"2009","journal-title":"Cell Motil. Cytoskeleton"},{"key":"B11","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. Royal Stat. Soc"},{"key":"B12","doi-asserted-by":"publisher","first-page":"12415","DOI":"10.1038\/s41598-018-30963-z","article-title":"UBXD1 is a mitochondrial recruitment factor for p97\/VCP and promotes mitophagy","volume":"8","author":"Bento","year":"2018","journal-title":"Sci. Rep"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"986","DOI":"10.4161\/auto.28390","article-title":"The role of GABARAPL1\/GEC1 in autophagic flux and mitochondrial quality control in MDA-MB-436 breast cancer cells","volume":"10","author":"Boyer-Guittaut","year":"2014","journal-title":"Autophagy"},{"key":"B15","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00401-006-0127-z","article-title":"Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry","volume":"112","author":"Braak","year":"2006","journal-title":"Acta Neuropathol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/BF00308809","article-title":"Neuropathological stageing of Alzheimer-related changes","volume":"82","author":"Braak","year":"1991","journal-title":"Acta Neuropathol"},{"key":"B17","unstructured":"BushnellB.\n          BBMap: A Fast, Accurate, Splice-Aware Aligner2014"},{"key":"B18","doi-asserted-by":"publisher","first-page":"150","DOI":"10.3390\/cells9010150","article-title":"Mitophagy in Alzheimer's disease and other age-related neurodegenerative diseases","volume":"9","author":"Cai","year":"2020","journal-title":"Cells"},{"key":"B19","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/ng2049","article-title":"Using FlyAtlas to identify better Drosophila melanogaster models of human disease","volume":"39","author":"Chintapalli","year":"2007","journal-title":"Nat. Genet"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan8821","article-title":"Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer's mouse model","volume":"361","author":"Choi","year":"2018","journal-title":"Science"},{"key":"B21","doi-asserted-by":"publisher","first-page":"D296","DOI":"10.1093\/nar\/gkx1067","article-title":"miRTarBase update 2018: A resource for experimentally validated microRNA-target interactions","volume":"46","author":"Chou","year":"2018","journal-title":"Nucl. Acids Res"},{"key":"B22","first-page":"40","article-title":"Transcription factor Sp1 inhibition, memory, and cytokines in a mouse model of Alzheimer's disease","volume":"4","author":"Citron","year":"2015","journal-title":"Am. J. Neurodegener. Dis"},{"key":"B23","doi-asserted-by":"publisher","first-page":"eaay8826","DOI":"10.1126\/science.aay8826","article-title":"Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau","volume":"370","author":"Darwich","year":"2020","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: A bridge between the Gene Expression Omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"B25","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/sdata.2018.142","article-title":"A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research","volume":"5","author":"De Jager","year":"2018","journal-title":"Sci. Data"},{"key":"B26","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s40035-019-0161-0","article-title":"Alzheimer's in a dish\u2013induced pluripotent stem cell-based disease modeling","volume":"8","author":"de Leeuw","year":"2019","journal-title":"Transl. Neurodegener"},{"key":"B27","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1038\/nrm3117","article-title":"ARF family G proteins and their regulators: Roles in membrane transport, development and disease","volume":"12","author":"Donaldson","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s40142-019-0157-1","article-title":"Sex Differences in the Genetic Architecture of Alzheimer's Disease","volume":"7","author":"Dumitrescu","year":"2019","journal-title":"Curr. Genet. Med. Rep"},{"key":"B29","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.ceb.2015.01.002","article-title":"PINK1\/Parkin-mediated mitophagy in mammalian cells","volume":"33","author":"Eiyama","year":"2015","journal-title":"Curr. Opin. Cell Biol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s41593-018-0332-9","article-title":"Mitophagy inhibits amyloid-beta and tau pathology and reverses cognitive deficits in models of Alzheimer's disease","volume":"22","author":"Fang","year":"2019","journal-title":"Nat. Neurosci"},{"key":"B31","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3389\/fncel.2015.00016","article-title":"Mitochondrial function in neuronal cells depends on p97\/VCP\/Cdc48-mediated quality control","volume":"9","author":"Fang","year":"2015","journal-title":"Front. Cell. Neurosci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"D766","DOI":"10.1093\/nar\/gky955","article-title":"GENCODE reference annotation for the human and mouse genomes","volume":"47","author":"Frankish","year":"2019","journal-title":"Nucl. Acids Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.celrep.2017.12.066","article-title":"Diverse brain myeloid expression profiles reveal distinct microglial activation states and aspects of alzheimer's disease not evident in mouse models","volume":"22","author":"Friedman","year":"2018","journal-title":"Cell Rep"},{"key":"B34","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13195-020-00623-4","article-title":"Alzheimer's disease progression characterized by alterations in the molecular profiles and biogenesis of brain extracellular vesicles","volume":"12","author":"Gallart-Palau","year":"2020","journal-title":"Alzheimer's Res. Ther"},{"key":"B35","doi-asserted-by":"publisher","first-page":"13970","DOI":"10.1038\/s41598-019-50035-0","article-title":"Identification of reference genes for RT-qPCR data normalisation in aging studies","volume":"9","author":"Gonz\u00e1lez-Berm\u00fadez","year":"2019","journal-title":"Sci. Rep"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e63133","DOI":"10.1371\/journal.pone.0063133","article-title":"Specific distribution of the autophagic protein GABARAPL1\/GEC1 in the developing and adult mouse brain and identification of neuronal populations expressing GABARAPL1\/GEC1","volume":"8","author":"Grand","year":"2013","journal-title":"PLoS ONE"},{"key":"B37","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.neubiorev.2016.04.012","article-title":"Alzheimer, mitochondria and gender","volume":"67","author":"Grimm","year":"2016","journal-title":"Neurosci. Biobehav. Rev"},{"key":"B38","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.biopsych.2021.02.968","article-title":"Sex Differences in Alzheimer's Disease: Insights From the Multiomics Landscape","volume":"91","author":"Guo","year":"2022","journal-title":"Biol. Psychiat"},{"key":"B39","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1517\/14728222.2016.1135132","article-title":"Accelerating medicines partnership: Alzheimer's disease (AMP-AD) knowledge portal aids Alzheimer's drug discovery through open data sharing","volume":"20","author":"Hodes","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"B40","doi-asserted-by":"publisher","first-page":"605961","DOI":"10.3389\/fnagi.2020.605961","article-title":"Co-expression network analysis reveals novel genes underlying Alzheimer's disease pathogenesis","volume":"12","author":"Hu","year":"2020","journal-title":"Front. Aging Neurosci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13195-017-0252-z","article-title":"Analyzing the genes related to Alzheimer's disease via a network and pathway-based approach","volume":"9","author":"Hu","year":"2017","journal-title":"Alz. Res. Therapy"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.15252\/emmm.201505256","article-title":"Impaired GAPDH-induced mitophagy contributes to the pathology of Huntington's disease","volume":"7","author":"Hwang","year":"2015","journal-title":"EMBO Molec. Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"D498","DOI":"10.1093\/nar\/gkz1031","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal","year":"2019","journal-title":"Nucl. Acids Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucl. Acids Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.tins.2017.01.002","article-title":"Mitophagy and Alzheimer's disease: cellular and molecular mechanisms","volume":"40","author":"Kerr","year":"2017","journal-title":"Trends Neurosci"},{"key":"B46","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1093\/bib\/bbs037","article-title":"Batch effect removal methods for microarray gene expression data integration: A survey","volume":"14","author":"Lazar","year":"2013","journal-title":"Brief Bioinform"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.4161\/auto.7.10.15904","article-title":"GABARAPL1 (GEC1): Original or copycat?","volume":"7","author":"Le Grand","year":"2011","journal-title":"Autophagy"},{"key":"B48","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1093\/nar\/gku864","article-title":"Svaseq: Removing batch effects and other unwanted noise from sequencing data","volume":"42","author":"Leek","year":"2014","journal-title":"Nucl. Acids Res"},{"key":"B49","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/alz.049209","article-title":"Late-onset schizophrenia and the competing risks of dementia and death: A national cohort study","volume":"17","author":"Levine","year":"2021","journal-title":"Alzheimer's Demen"},{"key":"B50","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.bbrc.2020.07.039","article-title":"Selective binding of mitophagy receptor protein Bcl-rambo to LC3\/GABARAP family proteins","volume":"530","author":"Li","year":"2020","journal-title":"Biochem. Biophys. Res. Commun"},{"key":"B51","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1038\/s41467-019-10101-7","article-title":"Epigenetic dysregulation of enhancers in neurons is associated with Alzheimer's disease pathology and cognitive symptoms","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun"},{"key":"B52","doi-asserted-by":"publisher","first-page":"4011","DOI":"10.1242\/jcs.03163","article-title":"Characterization of erasin (UBXD2): A new ER protein that promotes ER-associated protein degradation","volume":"119","author":"Liang","year":"2006","journal-title":"J. Cell Sci"},{"key":"B53","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","article-title":"Molecular signatures database (MSigDB) 3.0","volume":"27","author":"Liberzon","year":"2011","journal-title":"Bioinformatics"},{"key":"B55","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome. Biol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fgene.2014.00013","article-title":"On the optimal trimming of high-throughput mRNA sequence data","volume":"5","author":"MacManes","year":"2014","journal-title":"Front. Genet"},{"key":"B57","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.tibs.2020.11.007","article-title":"Mitochondrial dysfunction and mitophagy in Parkinson's disease: from mechanism to therapy","volume":"46","author":"Malpartida","year":"2021","journal-title":"Trends Biochem. Sci"},{"key":"B58","doi-asserted-by":"publisher","first-page":"5717","DOI":"10.1158\/1078-0432.CCR-19-1131","article-title":"Prognostic implications of PD-L1 expression in breast cancer: systematic review and meta-analysis of immunohistochemistry and pooled analysis of transcriptomic data","volume":"25","author":"Matikas","year":"2019","journal-title":"Clin. Cancer Res"},{"key":"B59","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2147\/CLEP.S37929","article-title":"Clinical epidemiology of Alzheimer's disease: Assessing sex and gender differences","volume":"6","author":"Mielke","year":"2014","journal-title":"CLEP"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.bbadis.2014.04.012","article-title":"Is Alzheimer's disease a systemic disease?","volume":"1842","author":"Morris","year":"2014","journal-title":"Molec. Basis Dis"},{"key":"B61","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/s41593-018-0101-9","article-title":"Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease","volume":"21","author":"Nativio","year":"2018","journal-title":"Nat. Neurosci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/embor.2009.256","article-title":"Nix is a selective autophagy receptor for mitochondrial clearance","volume":"11","author":"Novak","year":"2010","journal-title":"EMBO Rep"},{"key":"B63","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s40035-022-00308-y","article-title":"The use of fibroblasts as a valuable strategy for studying mitochondrial impairment in neurological disorders","volume":"11","author":"Olesen","year":"2022","journal-title":"Transl. Neurodegen"},{"key":"B64","doi-asserted-by":"publisher","first-page":"8716","DOI":"10.1038\/s41598-018-26707-8","article-title":"Validation of common housekeeping genes as reference for qPCR gene expression analysis during ips reprogramming process","volume":"8","author":"Panina","year":"2018","journal-title":"Sci. Rep"},{"key":"B65","doi-asserted-by":"publisher","first-page":"R1330","DOI":"10.1016\/j.cub.2017.11.012","article-title":"Detection and clearance of damaged lysosomes by the endo-lysosomal damage response and lysophagy","volume":"27","author":"Papadopoulos","year":"2017","journal-title":"Curr. Biol"},{"key":"B66","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.3233\/JAD-181085","article-title":"A meta-analysis of Alzheimer's disease brain transcriptomic data","volume":"68","author":"Patel","year":"2019","journal-title":"J. Alzheimers Dis"},{"key":"B67","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"B68","doi-asserted-by":"publisher","first-page":"5461","DOI":"10.3390\/ijms12095461","article-title":"Selection of candidate housekeeping genes for normalization in human postmortem brain samples","volume":"12","author":"Penna","year":"2011","journal-title":"IJMS"},{"key":"B69","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3390\/metabo10070286","article-title":"Find the needle in the haystack, then find it again: replication and validation in the \u2018omics era","volume":"10","author":"Perng","year":"2020","journal-title":"Metabolites"},{"key":"B70","doi-asserted-by":"publisher","first-page":"437","DOI":"10.31887\/DCNS.2016.18.4\/cepperson","article-title":"Considering sex and gender in Alzheimer disease and other dementias","volume":"18","author":"Podcasy","year":"2016","journal-title":"Dialog. Clin. Neurosci"},{"key":"B71","volume-title":"World Alzheimer Report 2014: Dementia and Risk Reduction - An Analysis of Protective and Modifiable Factors","author":"Prince","year":"2014"},{"key":"B72","volume-title":"World Alzheimer Report 2016: Improving healthcare for people living with dementia: Coverage, quality and costs now and in the future","author":"Prince","year":"2016"},{"key":"B73","volume-title":"World Alzheimer Report 2015: The Global Impact of Dementia: An Analysis of Prevalence, Incidence, Cost and Trends","author":"Prince","year":"2015"},{"key":"B74","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucl. Acids Res"},{"key":"B75","doi-asserted-by":"publisher","first-page":"10349","DOI":"10.1523\/JNEUROSCI.1409-18.2018","article-title":"Synaptotoxicity in Alzheimer's disease involved a dysregulation of actin cytoskeleton dynamics through cofilin 1 phosphorylation","volume":"38","author":"Rush","year":"2018","journal-title":"J. Neurosci"},{"key":"B76","doi-asserted-by":"publisher","first-page":"37116","DOI":"10.1038\/srep37116","article-title":"Assessment of brain reference genes for RT-qPCR studies in neurodegenerative diseases","volume":"6","author":"Rydbirk","year":"2016","journal-title":"Sci. Rep"},{"key":"B77","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/ni.3767","article-title":"Essential role for GABARAP autophagy proteins in interferon-inducible GTPase-mediated host defense","volume":"18","author":"Sasai","year":"2017","journal-title":"Nat. Immunol"},{"key":"B78","doi-asserted-by":"publisher","first-page":"3961","DOI":"10.1096\/fj.201600698R","article-title":"LC3\/GABARAP family proteins: Autophagy-(un)related functions","volume":"30","author":"Schaaf","year":"2016","journal-title":"The FASEB J"},{"key":"B79","doi-asserted-by":"publisher","first-page":"e10421","DOI":"10.7554\/eLife.10421","article-title":"Regulatory consequences of neuronal ELAV-like protein binding to coding and non-coding RNAs in human brain","volume":"5","author":"Scheckel","year":"2016","journal-title":"Elife"},{"key":"B80","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/s00401-018-1873-4","article-title":"Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson's models","volume":"136","author":"Shaltouki","year":"2018","journal-title":"Acta Neuropathol"},{"key":"B81","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Gen. Res"},{"key":"B82","doi-asserted-by":"publisher","first-page":"D661","DOI":"10.1093\/nar\/gkx1064","article-title":"WikiPathways: A multifaceted pathway database bridging metabolomics to other omics research","volume":"46","author":"Slenter","year":"2018","journal-title":"Nucl. Acids Res"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.12688\/f1000research.7563.2","article-title":"Differential analyses for RNA-seq: Transcript-level estimates improve gene-level inferences","volume":"4","author":"Soneson","year":"2016","journal-title":"F1000Res"},{"key":"B84","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3892\/ijo.2017.4212","article-title":"P-STAT3 in luminal breast cancer: Integrated RNA-protein pooled analysis and results from the BIG 2-98 phase III trial","volume":"52","author":"Sonnenblick","year":"2018","journal-title":"Int. J. Oncol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"107843","DOI":"10.1016\/j.celrep.2020.107843","article-title":"Alzheimer's patient microglia exhibit enhanced aging and unique transcriptional activation","volume":"31","author":"Srinivasan","year":"2020","journal-title":"Cell Rep"},{"key":"B86","doi-asserted-by":"publisher","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucl. Acids Res"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1016\/j.jalz.2019.06.4952","article-title":"Differential expression of microRNAs in Alzheimer's disease brain, blood, and cerebrospinal fluid","volume":"15","author":"Takousis","year":"2019","journal-title":"Alzheimers Dement"},{"key":"B88","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1186\/1471-2164-15-199","article-title":"Genomic convergence and network analysis approach to identify candidate genes in Alzheimer's disease","volume":"15","author":"Talwar","year":"2014","journal-title":"BMC Genom"},{"key":"B89","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1091\/mbc.E19-09-0487","article-title":"Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-\u03b2 production","volume":"31","author":"Tan","year":"2020","journal-title":"MBoC"},{"key":"B90","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1083\/jcb.201007013","article-title":"Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin","volume":"191","author":"Tanaka","year":"2010","journal-title":"J. Cell Biol"},{"key":"B91","doi-asserted-by":"publisher","first-page":"D330","DOI":"10.1093\/nar\/gky1055","article-title":"The Gene Ontology Resource: 20 years and still GOing strong","volume":"47","year":"2019","journal-title":"Nucl. Acids Res"},{"key":"B92","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S1474-4422(21)00031-4","article-title":"Genetic basis of lacunar stroke: A pooled analysis of individual patient data and genome-wide association studies","volume":"20","author":"Traylor","year":"2021","journal-title":"Lancet Neurol"},{"key":"B93","doi-asserted-by":"publisher","first-page":"487","DOI":"10.3233\/JAD-122263","article-title":"Expression of the transcription factor sp1 and its regulatory HSA-MIR-29b in peripheral blood mononuclear cells from patients with Alzheimer's disease","volume":"35","author":"Villa","year":"2013","journal-title":"JAD"},{"key":"B94","doi-asserted-by":"publisher","first-page":"107908","DOI":"10.1016\/j.celrep.2020.107908","article-title":"Meta-analysis of the Alzheimer's disease human brain transcriptome and functional dissection in mouse models","volume":"32","author":"Wan","year":"2020","journal-title":"Cell Rep"},{"key":"B95","doi-asserted-by":"publisher","first-page":"180185","DOI":"10.1038\/sdata.2018.185","article-title":"The Mount Sinai cohort of large-scale genomic, transcriptomic and proteomic data in Alzheimer's disease","volume":"5","author":"Wang","year":"2018","journal-title":"Sci. Data"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bav098","article-title":"miRSponge: A manually curated database for experimentally supported miRNA sponges and ceRNAs","author":"Wang","year":"2015","journal-title":"Database"},{"key":"B97","doi-asserted-by":"publisher","first-page":"970796","DOI":"10.3389\/fnagi.2022.970796","article-title":"Exploring the key ferroptosis-related gene in the peripheral blood of patients with Alzheimer's disease and its clinical significance","volume":"14","author":"Wang","year":"2022","journal-title":"Front. Aging Neurosci"},{"key":"B98","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.1093\/bioinformatics\/btz937","article-title":"ngsReports: A Bioconductor package for managing FastQC reports and other NGS related log files","volume":"36","author":"Ward","year":"2020","journal-title":"Bioinformatics"},{"key":"B99","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.jalz.2017.08.012","article-title":"A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer's disease","volume":"14","author":"Xu","year":"2018","journal-title":"Alzheimers Dement"},{"key":"B100","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1091\/mbc.e10-09-0748","article-title":"The AAA-ATPase p97 is essential for outer mitochondrial membrane protein turnover","volume":"22","author":"Xu","year":"2011","journal-title":"MBoC"},{"key":"B101","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.yjmcc.2016.03.010","article-title":"Receptor-mediated mitophagy","volume":"95","author":"Yamaguchi","year":"2016","journal-title":"J. Molec. Cell. Cardiol"},{"key":"B102","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R Package for Comparing Biological Themes Among Gene Clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B103","doi-asserted-by":"publisher","first-page":"602781","DOI":"10.3389\/fnagi.2021.602781","article-title":"Exploring the key genes and identification of potential diagnosis biomarkers in Alzheimer's disease using bioinformatics analysis","volume":"13","author":"Yu","year":"2021","journal-title":"Front. Aging Neurosci"},{"key":"B104","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1093\/bioinformatics\/btp295","article-title":"Evaluating reproducibility of differential expression discoveries in microarray studies by considering correlated molecular changes","volume":"25","author":"Zhang","year":"2009","journal-title":"Bioinformatics"},{"key":"B105","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.neuron.2013.05.029","article-title":"Rapid single-step induction of functional neurons from human pluripotent stem cells","volume":"78","author":"Zhang","year":"2013","journal-title":"Neuron"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2023.1101216\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T05:05:02Z","timestamp":1686287102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2023.1101216\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,9]]},"references-count":105,"alternative-id":["10.3389\/fnagi.2023.1101216"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2023.1101216","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,9]]},"article-number":"1101216"}}