Academic Journal
أعرض في EDS

Differential Effects of APOE Genotype on MicroRNA Cargo of Cerebrospinal Fluid Extracellular Vesicles in Females With Alzheimer’s Disease Compared to Males

التفاصيل البيبلوغرافية
العنوان: Differential Effects of APOE Genotype on MicroRNA Cargo of Cerebrospinal Fluid Extracellular Vesicles in Females With Alzheimer’s Disease Compared to Males
المؤلفون: Ursula S. Sandau, Trevor J. McFarland, Sierra J. Smith, Douglas R. Galasko, Joseph F. Quinn, Julie A. Saugstad
المصدر: Frontiers in Cell and Developmental Biology, Vol 10 (2022)
بيانات النشر: Frontiers Media S.A., 2022.
سنة النشر: 2022
المجموعة: LCC:Biology (General)
مصطلحات موضوعية: Alzheimer’s disease, cerebrospinal fluid (CSF), extracellular vesicle (EV), microRNA, apolipoprotein E allele (APOE), sex difference, Biology (General), QH301-705.5
الوصف: Multiple biological factors, including age, sex, and genetics, influence Alzheimer’s disease (AD) risk. Of the 6.2 million Americans living with Alzheimer’s dementia in 2021, 3.8 million are women and 2.4 million are men. The strongest genetic risk factor for sporadic AD is apolipoprotein E-e4 (APOE-e4). Female APOE-e4 carriers develop AD more frequently than age-matched males and have more brain atrophy and memory loss. Consequently, biomarkers that are sensitive to biological risk factors may improve AD diagnostics and may provide insight into underlying mechanistic changes that could drive disease progression. Here, we have assessed the effects of sex and APOE-e4 on the miRNA cargo of cerebrospinal fluid (CSF) extracellular vesicles (EVs) in AD. We used ultrafiltration (UF) combined with size exclusion chromatography (SEC) to enrich CSF EVs (e.g., Flotillin+). CSF EVs were isolated from female and male AD or controls (CTLs) that were either APOE-e3,4 or -e3,3 positive (n = 7/group, 56 total). MiRNA expression levels were quantified using a custom TaqMan™ array that assayed 190 miRNAs previously found in CSF, including 25 miRNAs that we previously validated as candidate AD biomarkers. We identified changes in the EV miRNA cargo that were affected by both AD and sex. In total, four miRNAs (miR-16-5p, -331-3p, -409-3p, and -454-3p) were significantly increased in AD vs. CTL, independent of sex and APOE-e4 status. Pathway analysis of the predicted gene targets of these four miRNAs with identified pathways was highly relevant to neurodegeneration (e.g., senescence and autophagy). There were also three miRNAs (miR-146b-5p, -150-5p, and -342-3p) that were significantly increased in females vs. males, independent of disease state and APOE-e4 status. We then performed a statistical analysis to assess the effect of APOE genotype in AD within each sex and found that APOE-e4 status affects different subsets of CSF EV miRNAs in females vs. males. Together, this study demonstrates the complexity of the biological factors associated with AD risk and the impact on EV miRNAs, which may contribute to AD pathophysiology.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2296-634X
Relation: https://www.frontiersin.org/articles/10.3389/fcell.2022.864022/full; https://doaj.org/toc/2296-634X
DOI: 10.3389/fcell.2022.864022
URL الوصول: https://doaj.org/article/f4310d878732436c8a496384bba74a78
رقم الانضمام: edsdoj.f4310d878732436c8a496384bba74a78
قاعدة البيانات: Directory of Open Access Journals
ResultId 1
Header edsdoj
Directory of Open Access Journals
edsdoj.f4310d878732436c8a496384bba74a78
942
3
Academic Journal
academicJournal
942.363525390625
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsdoj&AN=edsdoj.f4310d878732436c8a496384bba74a78&custid=s6537998&authtype=sso
FullText Array ( [Availability] => 0 )
Array ( [0] => Array ( [Url] => https://doaj.org/article/f4310d878732436c8a496384bba74a78 [Name] => EDS - DOAJ [Category] => fullText [Text] => View record in DOAJ [MouseOverText] => View record in DOAJ ) [1] => Array ( [Url] => https://resolver.ebscohost.com/openurl?custid=s6537998&groupid=main&authtype=ip,guest&sid=EBSCO:edsdoj&genre=article&issn=2296634X&ISBN=&volume=10&issue=&date=20220401&spage=&pages=&title=Frontiers in Cell and Developmental Biology&atitle=Differential%20Effects%20of%20APOE%20Genotype%20on%20MicroRNA%20Cargo%20of%20Cerebrospinal%20Fluid%20Extracellular%20Vesicles%20in%20Females%20With%20Alzheimer%E2%80%99s%20Disease%20Compared%20to%20Males&id=DOI:10.3389/fcell.2022.864022 [Name] => Full Text Finder (s6537998api) [Category] => fullText [Text] => Full Text Finder [Icon] => https://imageserver.ebscohost.com/branding/images/FTF.gif [MouseOverText] => Full Text Finder ) )
Items Array ( [Name] => Title [Label] => Title [Group] => Ti [Data] => Differential Effects of APOE Genotype on MicroRNA Cargo of Cerebrospinal Fluid Extracellular Vesicles in Females With Alzheimer’s Disease Compared to Males )
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Ursula+S%2E+Sandau%22">Ursula S. Sandau</searchLink><br /><searchLink fieldCode="AR" term="%22Trevor+J%2E+McFarland%22">Trevor J. McFarland</searchLink><br /><searchLink fieldCode="AR" term="%22Sierra+J%2E+Smith%22">Sierra J. Smith</searchLink><br /><searchLink fieldCode="AR" term="%22Douglas+R%2E+Galasko%22">Douglas R. Galasko</searchLink><br /><searchLink fieldCode="AR" term="%22Joseph+F%2E+Quinn%22">Joseph F. Quinn</searchLink><br /><searchLink fieldCode="AR" term="%22Julie+A%2E+Saugstad%22">Julie A. Saugstad</searchLink> )
Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => Frontiers in Cell and Developmental Biology, Vol 10 (2022) )
Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Frontiers Media S.A., 2022. )
Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2022 )
Array ( [Name] => Subset [Label] => Collection [Group] => HoldingsInfo [Data] => LCC:Biology (General) )
Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22Alzheimer%27s+disease%22">Alzheimer’s disease</searchLink><br /><searchLink fieldCode="DE" term="%22cerebrospinal+fluid+%28CSF%29%22">cerebrospinal fluid (CSF)</searchLink><br /><searchLink fieldCode="DE" term="%22extracellular+vesicle+%28EV%29%22">extracellular vesicle (EV)</searchLink><br /><searchLink fieldCode="DE" term="%22microRNA%22">microRNA</searchLink><br /><searchLink fieldCode="DE" term="%22apolipoprotein+E+allele+%28APOE%29%22">apolipoprotein E allele (APOE)</searchLink><br /><searchLink fieldCode="DE" term="%22sex+difference%22">sex difference</searchLink><br /><searchLink fieldCode="DE" term="%22Biology+%28General%29%22">Biology (General)</searchLink><br /><searchLink fieldCode="DE" term="%22QH301-705%2E5%22">QH301-705.5</searchLink> )
Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => Multiple biological factors, including age, sex, and genetics, influence Alzheimer’s disease (AD) risk. Of the 6.2 million Americans living with Alzheimer’s dementia in 2021, 3.8 million are women and 2.4 million are men. The strongest genetic risk factor for sporadic AD is apolipoprotein E-e4 (APOE-e4). Female APOE-e4 carriers develop AD more frequently than age-matched males and have more brain atrophy and memory loss. Consequently, biomarkers that are sensitive to biological risk factors may improve AD diagnostics and may provide insight into underlying mechanistic changes that could drive disease progression. Here, we have assessed the effects of sex and APOE-e4 on the miRNA cargo of cerebrospinal fluid (CSF) extracellular vesicles (EVs) in AD. We used ultrafiltration (UF) combined with size exclusion chromatography (SEC) to enrich CSF EVs (e.g., Flotillin+). CSF EVs were isolated from female and male AD or controls (CTLs) that were either APOE-e3,4 or -e3,3 positive (n = 7/group, 56 total). MiRNA expression levels were quantified using a custom TaqMan™ array that assayed 190 miRNAs previously found in CSF, including 25 miRNAs that we previously validated as candidate AD biomarkers. We identified changes in the EV miRNA cargo that were affected by both AD and sex. In total, four miRNAs (miR-16-5p, -331-3p, -409-3p, and -454-3p) were significantly increased in AD vs. CTL, independent of sex and APOE-e4 status. Pathway analysis of the predicted gene targets of these four miRNAs with identified pathways was highly relevant to neurodegeneration (e.g., senescence and autophagy). There were also three miRNAs (miR-146b-5p, -150-5p, and -342-3p) that were significantly increased in females vs. males, independent of disease state and APOE-e4 status. We then performed a statistical analysis to assess the effect of APOE genotype in AD within each sex and found that APOE-e4 status affects different subsets of CSF EV miRNAs in females vs. males. Together, this study demonstrates the complexity of the biological factors associated with AD risk and the impact on EV miRNAs, which may contribute to AD pathophysiology. )
Array ( [Name] => TypeDocument [Label] => Document Type [Group] => TypDoc [Data] => article )
Array ( [Name] => Format [Label] => File Description [Group] => SrcInfo [Data] => electronic resource )
Array ( [Name] => Language [Label] => Language [Group] => Lang [Data] => English )
Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 2296-634X )
Array ( [Name] => NoteTitleSource [Label] => Relation [Group] => SrcInfo [Data] => https://www.frontiersin.org/articles/10.3389/fcell.2022.864022/full; https://doaj.org/toc/2296-634X )
Array ( [Name] => DOI [Label] => DOI [Group] => ID [Data] => 10.3389/fcell.2022.864022 )
Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://doaj.org/article/f4310d878732436c8a496384bba74a78" linkWindow="_blank">https://doaj.org/article/f4310d878732436c8a496384bba74a78</link> )
Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsdoj.f4310d878732436c8a496384bba74a78 )
RecordInfo Array ( [BibEntity] => Array ( [Identifiers] => Array ( [0] => Array ( [Type] => doi [Value] => 10.3389/fcell.2022.864022 ) ) [Languages] => Array ( [0] => Array ( [Text] => English ) ) [Subjects] => Array ( [0] => Array ( [SubjectFull] => Alzheimer’s disease [Type] => general ) [1] => Array ( [SubjectFull] => cerebrospinal fluid (CSF) [Type] => general ) [2] => Array ( [SubjectFull] => extracellular vesicle (EV) [Type] => general ) [3] => Array ( [SubjectFull] => microRNA [Type] => general ) [4] => Array ( [SubjectFull] => apolipoprotein E allele (APOE) [Type] => general ) [5] => Array ( [SubjectFull] => sex difference [Type] => general ) [6] => Array ( [SubjectFull] => Biology (General) [Type] => general ) [7] => Array ( [SubjectFull] => QH301-705.5 [Type] => general ) ) [Titles] => Array ( [0] => Array ( [TitleFull] => Differential Effects of APOE Genotype on MicroRNA Cargo of Cerebrospinal Fluid Extracellular Vesicles in Females With Alzheimer’s Disease Compared to Males [Type] => main ) ) ) [BibRelationships] => Array ( [HasContributorRelationships] => Array ( [0] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Ursula S. Sandau ) ) ) [1] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Trevor J. McFarland ) ) ) [2] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Sierra J. Smith ) ) ) [3] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Douglas R. Galasko ) ) ) [4] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Joseph F. Quinn ) ) ) [5] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Julie A. Saugstad ) ) ) ) [IsPartOfRelationships] => Array ( [0] => Array ( [BibEntity] => Array ( [Dates] => Array ( [0] => Array ( [D] => 01 [M] => 04 [Type] => published [Y] => 2022 ) ) [Identifiers] => Array ( [0] => Array ( [Type] => issn-print [Value] => 2296634X ) ) [Numbering] => Array ( [0] => Array ( [Type] => volume [Value] => 10 ) ) [Titles] => Array ( [0] => Array ( [TitleFull] => Frontiers in Cell and Developmental Biology [Type] => main ) ) ) ) ) ) )
IllustrationInfo