000259715 001__ 259715
000259715 005__ 20240403113241.0
000259715 0247_ $$2doi$$a10.1111/acel.13871
000259715 0247_ $$2pmid$$apmid:37291760
000259715 0247_ $$2pmc$$apmc:PMC10410059
000259715 0247_ $$2ISSN$$a1474-9718
000259715 0247_ $$2ISSN$$a1474-9726
000259715 0247_ $$2ISSN$$a1474-9728
000259715 0247_ $$2altmetric$$aaltmetric:149779355
000259715 037__ $$aDZNE-2023-00787
000259715 041__ $$aEnglish
000259715 082__ $$a610
000259715 1001_ $$00000-0001-8460-4415$$aSchultz, Stephanie A$$b0
000259715 245__ $$aLocation of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal-dominant Alzheimer's disease.
000259715 260__ $$aOxford [u.a.]$$bWiley-Blackwell$$c2023
000259715 3367_ $$2DRIVER$$aarticle
000259715 3367_ $$2DataCite$$aOutput Types/Journal article
000259715 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1694011611_1589
000259715 3367_ $$2BibTeX$$aARTICLE
000259715 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000259715 3367_ $$00$$2EndNote$$aJournal Article
000259715 520__ $$aAlthough pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection of cerebrospinal fluid (CSF) as part of their participation in DIAN were included in this study. Linear mixed effects models were used to determine differences in clinical, cognitive, and biomarker measures between the NC, TM, and CY groups. While both the CY and TM groups were found to have similarly elevated Aβ compared to NC, TM carriers had greater cognitive impairment, smaller hippocampal volume, and elevated phosphorylated tau levels across the spectrum of pre-symptomatic and symptomatic phases of disease as compared to CY, using both cross-sectional and longitudinal data. As distinct portions of PSEN1 are differentially involved in APP processing by γ-secretase and the generation of toxic β-amyloid species, these results have important implications for understanding the pathobiology of ADAD and accounting for a substantial portion of the interindividual heterogeneity in ongoing ADAD clinical trials.
000259715 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000259715 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1
000259715 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000259715 650_2 $$2MeSH$$aMale
000259715 650_2 $$2MeSH$$aHumans
000259715 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000259715 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000259715 650_2 $$2MeSH$$aCross-Sectional Studies
000259715 650_2 $$2MeSH$$aAmyloid beta-Peptides: genetics
000259715 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000259715 650_2 $$2MeSH$$aBiomarkers
000259715 650_2 $$2MeSH$$aPresenilin-1: genetics
000259715 650_2 $$2MeSH$$aCognition
000259715 650_2 $$2MeSH$$aMutation
000259715 650_2 $$2MeSH$$aFemale
000259715 650_2 $$2MeSH$$aAdult
000259715 650_2 $$2MeSH$$aBrain: metabolism
000259715 650_2 $$2MeSH$$aBrain: pathology
000259715 650_2 $$2MeSH$$aPositron-Emission Tomography
000259715 650_2 $$2MeSH$$aMagnetic Resonance Imaging
000259715 650_2 $$2MeSH$$aPresenilin-1: chemistry
000259715 650_2 $$2MeSH$$aPresenilin-1: metabolism
000259715 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000259715 650_2 $$2MeSH$$atau Proteins: metabolism
000259715 650_2 $$2MeSH$$aLongitudinal Studies
000259715 650_7 $$2Other$$aPSEN1
000259715 650_7 $$2NLM Chemicals$$atau Proteins
000259715 650_7 $$2Other$$a PSEN1 
000259715 650_7 $$2Other$$a Presenilin-1 
000259715 650_7 $$2Other$$aAutosomal dominant Alzheimer disease (ADAD)
000259715 650_7 $$2Other$$aheterogeneity
000259715 650_7 $$2Other$$aneurodegeneration
000259715 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000259715 650_7 $$2NLM Chemicals$$aBiomarkers
000259715 650_7 $$2NLM Chemicals$$aPresenilin-1
000259715 650_7 $$2NLM Chemicals$$aPSEN1 protein, human
000259715 650_7 $$2Other$$aPresenilin-1
000259715 693__ $$0EXP:(DE-2719)DIAN-20090101$$5EXP:(DE-2719)DIAN-20090101$$eLongitudinal Study on Dominantly Inherited Alzheimer's Disease$$x0
000259715 7001_ $$aShirzadi, Zahra$$b1
000259715 7001_ $$aSchultz, Aaron P$$b2
000259715 7001_ $$00000-0002-4604-4629$$aLiu, Lei$$b3
000259715 7001_ $$aFitzpatrick, Colleen D$$b4
000259715 7001_ $$aMcDade, Eric$$b5
000259715 7001_ $$aBarthelemy, Nicolas R$$b6
000259715 7001_ $$aRenton, Alan$$b7
000259715 7001_ $$aEsposito, Bianca$$b8
000259715 7001_ $$aJoseph-Mathurin, Nelly$$b9
000259715 7001_ $$aCruchaga, Carlos$$b10
000259715 7001_ $$aChen, Charles D$$b11
000259715 7001_ $$aGoate, Alison$$b12
000259715 7001_ $$aAllegri, Ricardo Francisco$$b13
000259715 7001_ $$aBenzinger, Tammie L S$$b14
000259715 7001_ $$aBerman, Sarah$$b15
000259715 7001_ $$aChui, Helena C$$b16
000259715 7001_ $$aFagan, Anne M$$b17
000259715 7001_ $$aFarlow, Martin R$$b18
000259715 7001_ $$aFox, Nick C$$b19
000259715 7001_ $$aGordon, Brian A$$b20
000259715 7001_ $$aDay, Gregory S$$b21
000259715 7001_ $$aGraff-Radford, Neill R$$b22
000259715 7001_ $$aHassenstab, Jason J$$b23
000259715 7001_ $$aHanseeuw, Bernard J$$b24
000259715 7001_ $$0P:(DE-2719)2814244$$aHofmann, Anna$$b25$$udzne
000259715 7001_ $$aJack, Clifford R$$b26
000259715 7001_ $$0P:(DE-2719)2000010$$aJucker, Mathias$$b27$$udzne
000259715 7001_ $$aKarch, Celeste M$$b28
000259715 7001_ $$aKoeppe, Robert A$$b29
000259715 7001_ $$0P:(DE-HGF)0$$aLee, Jae-Hong$$b30
000259715 7001_ $$aLevey, Allan I$$b31
000259715 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b32$$udzne
000259715 7001_ $$aMartins, Ralph N$$b33
000259715 7001_ $$aMori, Hiroshi$$b34
000259715 7001_ $$aMorris, John C$$b35
000259715 7001_ $$aNoble, James$$b36
000259715 7001_ $$aPerrin, Richard J$$b37
000259715 7001_ $$aRosa-Neto, Pedro$$b38
000259715 7001_ $$aSalloway, Stephen P$$b39
000259715 7001_ $$aSanchez-Valle, Raquel$$b40
000259715 7001_ $$aSchofield, Peter R$$b41
000259715 7001_ $$aXiong, Chengjie$$b42
000259715 7001_ $$aJohnson, Keith A$$b43
000259715 7001_ $$aBateman, Randall J$$b44
000259715 7001_ $$aSperling, Reisa A$$b45
000259715 7001_ $$aChhatwal, Jasmeer P$$b46
000259715 7001_ $$aInvestigators, Dominantly Inherited Alzheimer Network$$b47$$eCollaboration Author
000259715 773__ $$0PERI:(DE-600)2099130-7$$a10.1111/acel.13871$$gVol. 22, no. 8, p. e13871$$n8$$pe13871$$tAging cell$$v22$$x1474-9718$$y2023
000259715 8564_ $$uhttps://pub.dzne.de/record/259715/files/DZNE-2023-00787.pdf$$yOpenAccess
000259715 8564_ $$uhttps://pub.dzne.de/record/259715/files/DZNE-2023-00787.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000259715 909CO $$ooai:pub.dzne.de:259715$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000259715 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2814244$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b25$$kDZNE
000259715 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000010$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b27$$kDZNE
000259715 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811659$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b32$$kDZNE
000259715 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0
000259715 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x1
000259715 9141_ $$y2023
000259715 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2022-11-08
000259715 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2022-11-08
000259715 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2022-11-08
000259715 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2022-11-08
000259715 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000259715 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2022-11-08
000259715 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000259715 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bAGING CELL : 2022$$d2023-08-29
000259715 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-29
000259715 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-29
000259715 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-08-29
000259715 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2022-12-27T13:17:21Z
000259715 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2022-12-27T13:17:21Z
000259715 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Peer review$$d2022-12-27T13:17:21Z
000259715 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2023-08-29
000259715 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2023-08-29
000259715 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-29
000259715 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-08-29
000259715 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-29
000259715 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bAGING CELL : 2022$$d2023-08-29
000259715 9201_ $$0I:(DE-2719)1210000$$kAG Gasser$$lParkinson Genetics$$x0
000259715 9201_ $$0I:(DE-2719)1210001$$kAG Jucker$$lCell Biology of Neurological Diseases$$x1
000259715 9201_ $$0I:(DE-2719)1111016$$kAG Levin$$lClinical Neurodegeneration$$x2
000259715 9201_ $$0I:(DE-2719)1111015$$kClinical Research (Munich)$$lClinical Research (Munich)$$x3
000259715 980__ $$ajournal
000259715 980__ $$aVDB
000259715 980__ $$aUNRESTRICTED
000259715 980__ $$aI:(DE-2719)1210000
000259715 980__ $$aI:(DE-2719)1210001
000259715 980__ $$aI:(DE-2719)1111016
000259715 980__ $$aI:(DE-2719)1111015
000259715 9801_ $$aFullTexts