{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T22:55:20Z","timestamp":1782600920511,"version":"3.54.5"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014191","name":"Brain Research New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001511","name":"Auckland Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001511","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Gene expression studies of human <jats:italic>post-mortem<\/jats:italic> brain tissue are useful for understanding the pathogenesis of neurodegenerative disease. These studies rely on the assumption that RNA quality is consistent between disease and neurologically normal cases; however, previous studies have suggested that RNA quality may be affected by neurodegenerative disease. Here, we compared RNA quality in human <jats:italic>post-mortem<\/jats:italic> brain tissue between neurologically normal cases (<jats:italic>n<\/jats:italic> = 14) and neurodegenerative disease cases (Alzheimer\u2019s disease <jats:italic>n<\/jats:italic> = 10; Parkinson\u2019s disease <jats:italic>n<\/jats:italic> = 11; and Huntington\u2019s disease <jats:italic>n<\/jats:italic> = 9) in regions affected by pathology and regions that are relatively devoid of pathology. We identified a statistically significant decrease in RNA integrity number (RIN) in Alzheimer\u2019s disease tissue relative to neurologically normal tissue (mixed effects model, <jats:italic>p<\/jats:italic> = 0.04). There were no statistically significant differences between neurologically normal cases and Parkinson\u2019s disease or Huntington\u2019s disease cases. Next, we investigated whether total RNA quality affected mRNA quantification, by correlating RIN with qPCR threshold cycle (C<jats:sub>T<\/jats:sub>). C<jats:sub>T<\/jats:sub> values for all six genes investigated were strongly correlated with RIN (<jats:italic>p<\/jats:italic> &amp;lt; 0.05, Pearson correlation); this effect was only partially mitigated by normalization to RPL30. Our results indicate that RNA quality is decreased in Alzheimer\u2019s disease tissue. We recommend that RIN should be considered when this tissue is used in gene expression analyses.<\/jats:p>","DOI":"10.3389\/fnmol.2021.780352","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T05:59:16Z","timestamp":1640066356000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["RNA Quality in Post-mortem Human Brain Tissue Is Affected by Alzheimer\u2019s Disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Blake","family":"Highet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remai","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L. M.","family":"Faull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice A.","family":"Curtis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigid","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.neuint.2006.01.018","article-title":"TaqMan PCR assay in the control of RNA normalization in human post-mortem brain tissue.","volume":"49","author":"Barrachina","year":"2006","journal-title":"Neurochem. Int."},{"key":"B2","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s10561-010-9210-8","article-title":"Postmortem interval effect on RNA and gene expression in human brain tissue.","volume":"12","author":"Birdsill","year":"2011","journal-title":"Cell Tissue Bank"},{"key":"B3","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.yexmp.2007.08.019","article-title":"Assessing RNA quality in postmortem human brain tissue.","volume":"84","author":"Chevyreva","year":"2008","journal-title":"Exp. Mol. Pathol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1007\/s12035-015-9105-6","article-title":"Analysis of RNA from Alzheimer\u2019s disease post-mortem brain tissues.","volume":"53","author":"Clement","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/1471-2199-9-46","article-title":"Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue.","volume":"9","author":"Coulson","year":"2008","journal-title":"BMC Mol. Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2311","DOI":"10.1038\/s41467-021-22399-3","article-title":"Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer\u2019s disease.","volume":"12","author":"Crist","year":"2021","journal-title":"Nat. Commun."},{"key":"B7","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.neurobiolaging.2020.12.007","article-title":"Decreased pH in the aging brain and Alzheimer\u2019s disease.","volume":"101","author":"Decker","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"B8","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences.","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"B9","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.mam.2005.12.003","article-title":"RNA integrity and the effect on the real-time qRT-PCR performance.","volume":"27","author":"Fleige","year":"2006","journal-title":"Mol. Aspects Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"4865","DOI":"10.1038\/s41598-021-83872-z","article-title":"Defining early changes in Alzheimer\u2019s disease from RNA sequencing of brain regions differentially affected by pathology.","volume":"11","author":"Guennewig","year":"2021","journal-title":"Sci. Rep."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1111\/jnc.15283","article-title":"fISHing with immunohistochemistry for housekeeping gene changes in Alzheimer\u2019s disease using an automated quantitative analysis workflow.","volume":"157","author":"Highet","year":"2021","journal-title":"J. Neurochem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method.","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B13","doi-asserted-by":"publisher","first-page":"82323","DOI":"10.1155\/JBB\/2006\/82323","article-title":"Oxidative damage to RNA in neurodegenerative diseases.","volume":"2006","author":"Nunomura","year":"2006","journal-title":"J. Biomed. Biotechnol."},{"key":"B14","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":"Int. J. Mol. Sci."},{"key":"B15","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":"B16","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1111\/j.1365-2990.2011.01163.x","article-title":"A new index of agonal state for neurological disease.","volume":"37","author":"Sherwood","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1111\/j.1365-2990.2011.01162.x","article-title":"RNA integrity in post mortem human variant Creutzfeldt-Jakob disease (vCJD) and control brain tissue.","volume":"37","author":"Sherwood","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.biopsych.2003.10.013","article-title":"Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain.","volume":"55","author":"Tomita","year":"2004","journal-title":"Biol. Psychiatry"},{"key":"B19","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.biopsych.2010.05.023","article-title":"Changed relative to what? Housekeeping genes and normalization strategies in human brain gene expression studies.","volume":"69","author":"Tunbridge","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1038\/nprot.2006.354","article-title":"Immunohistochemical staining of post-mortem adult human brain sections.","volume":"1","author":"Waldvogel","year":"2006","journal-title":"Nat. Protoc."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0079-6123(06)58001-X","article-title":"Tissue preparation and banking.","volume":"158","author":"Webster","year":"2006","journal-title":"Funct. Genomics Proteomics Clin. Neurosci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1089\/bio.2017.0099","article-title":"Effect of postmortem interval and years in storage on RNA quality of tissue at a repository of the NIH neurobiobank.","volume":"16","author":"White","year":"2018","journal-title":"Biopreserv. Biobank."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2021.780352\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T05:59:22Z","timestamp":1640066362000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2021.780352\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,21]]},"references-count":22,"alternative-id":["10.3389\/fnmol.2021.780352"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2021.780352","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,21]]},"article-number":"780352"}}