000269526 001__ 269526
000269526 005__ 20240926143148.0
000269526 0247_ $$2doi$$a10.1001/jamaneurol.2024.0991
000269526 0247_ $$2ISSN$$a2168-6149
000269526 0247_ $$2ISSN$$a0003-9942
000269526 0247_ $$2ISSN$$a0375-8540
000269526 0247_ $$2ISSN$$a1538-3687
000269526 0247_ $$2ISSN$$a2168-6157
000269526 0247_ $$2ISSN$$a2330-9644
000269526 0247_ $$2altmetric$$aaltmetric:162965095
000269526 0247_ $$2pmid$$apmid:38683602
000269526 037__ $$aDZNE-2024-00567
000269526 041__ $$aEnglish
000269526 082__ $$a610
000269526 1001_ $$0P:(DE-2719)9001249$$aWagemann, Olivia$$b0
000269526 245__ $$aDownstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease
000269526 260__ $$aChicago, Ill.$$bAmerican Medical Association$$c2024
000269526 3367_ $$2DRIVER$$aarticle
000269526 3367_ $$2DataCite$$aOutput Types/Journal article
000269526 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1718177351_28349
000269526 3367_ $$2BibTeX$$aARTICLE
000269526 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000269526 3367_ $$00$$2EndNote$$aJournal Article
000269526 520__ $$aImportance  Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD).Objective  To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment.Design, Setting, and Participants  From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD. Carriers of gene variants were assigned 3:1 to either drug or placebo. The present analysis was conducted from April to June 2023. DIAN-TU-001 spans 25 study sites in 7 countries. Biofluids and neuroimaging from carriers of DIAD gene variants in the gantenerumab, solanezumab, and placebo groups were analyzed.Interventions  In 2016, initial dosing of gantenerumab, 225 mg (subcutaneously every 4 weeks) was increased every 8 weeks up to 1200 mg. In 2017, initial dosing of solanezumab, 400 mg (intravenously every 4 weeks) was increased up to 1600 mg every 4 weeks.Main Outcomes and Measures  Longitudinal changes in CSF levels of neurogranin, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3–like 1 protein (YKL-40), glial fibrillary acidic protein (GFAP), neurofilament light protein (NfL), and plasma levels of GFAP and NfL.Results  Of 236 eligible participants screened, 43 were excluded. A total of 142 participants (mean [SD] age, 44 [10] years; 72 female [51%]) were included in the study (gantenerumab, 52 [37%]; solanezumab, 50 [35%]; placebo, 40 [28%]). Relative to placebo, gantenerumab significantly reduced CSF neurogranin level at year 4 (mean [SD] β = −242.43 [48.04] pg/mL; P < .001); reduced plasma GFAP level at year 1 (mean [SD] β = −0.02 [0.01] ng/mL; P = .02), year 2 (mean [SD] β = −0.03 [0.01] ng/mL; P = .002), and year 4 (mean [SD] β = −0.06 [0.02] ng/mL; P < .001); and increased CSF sTREM2 level at year 2 (mean [SD] β = 1.12 [0.43] ng/mL; P = .01) and year 4 (mean [SD] β = 1.06 [0.52] ng/mL; P = .04). Solanezumab significantly increased CSF NfL (log) at year 4 (mean [SD] β = 0.14 [0.06]; P = .02). Correlation analysis for rates of change found stronger correlations between CSF markers and fluid markers with Pittsburgh compound B positron emission tomography for solanezumab and placebo.Conclusions and Relevance  This randomized clinical trial supports the importance of fibrillar amyloid reduction in multiple AD-related processes of neuroinflammation and neurodegeneration in CSF and plasma in DIAD. Additional studies of antiaggregated amyloid therapies in sporadic AD and DIAD are needed to determine the utility of nonamyloid biomarkers in determining disease modification.</br><b>Key Points</b>Question  How do antiamyloid agents affect downstream biomarkers of Alzheimer-related pathophysiology regarding their target engagement with either soluble (solanezumab) or fibrillar (gantenerumab) amyloid?Findings  This phase 2/3 double-blind, placebo-controlled, randomized clinical trial including 142 participants investigated gantenerumab and solanezumab in individuals with gene variants for dominantly inherited Alzheimer disease. Gantenerumab decreased cerebrospinal fluid (CSF) neurogranin and plasma glial fibrillary acidic protein levels while increasing CSF levels of soluble triggering receptor expressed on myeloid cells 2; in contrast, solanezumab treatment was associated with increased CSF neurofilament light protein levels.Meaning  Antiamyloid agents removing fibrillar amyloid plaques demonstrated effects on glial and postsynaptic fluid biomarkers downstream of initial amyloid deposition, whereas binding soluble amyloid-β was associated with increased measures of neurodegeneration.
000269526 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0
000269526 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1
000269526 588__ $$aDataset connected to CrossRef, Journals: pub.dzne.de
000269526 7001_ $$aLiu, Haiyan$$b1
000269526 7001_ $$aWang, Guoqiao$$b2
000269526 7001_ $$aShi, Xinyu$$b3
000269526 7001_ $$0P:(DE-2719)9000029$$aBittner, Tobias$$b4
000269526 7001_ $$aScelsi, Marzia A.$$b5
000269526 7001_ $$aFarlow, Martin R.$$b6
000269526 7001_ $$aClifford, David B.$$b7
000269526 7001_ $$aSupnet-Bell, Charlene$$b8
000269526 7001_ $$aSantacruz, Anna M.$$b9
000269526 7001_ $$aAschenbrenner, Andrew J.$$b10
000269526 7001_ $$aHassenstab, Jason J.$$b11
000269526 7001_ $$aBenzinger, Tammie L. S.$$b12
000269526 7001_ $$aGordon, Brian A.$$b13
000269526 7001_ $$aCoalier, Kelley A.$$b14
000269526 7001_ $$aCruchaga, Carlos$$b15
000269526 7001_ $$aIbanez, Laura$$b16
000269526 7001_ $$aPerrin, Richard J.$$b17
000269526 7001_ $$aXiong, Chengjie$$b18
000269526 7001_ $$aLi, Yan$$b19
000269526 7001_ $$aMorris, John C.$$b20
000269526 7001_ $$aLah, James J.$$b21
000269526 7001_ $$aBerman, Sarah B.$$b22
000269526 7001_ $$aRoberson, Erik D.$$b23
000269526 7001_ $$avan Dyck, Christopher H.$$b24
000269526 7001_ $$aGalasko, Douglas$$b25
000269526 7001_ $$aGauthier, Serge$$b26
000269526 7001_ $$aHsiung, Ging-Yuek R.$$b27
000269526 7001_ $$aBrooks, William S.$$b28
000269526 7001_ $$aPariente, Jérémie$$b29
000269526 7001_ $$aMummery, Catherine J.$$b30
000269526 7001_ $$aDay, Gregory S.$$b31
000269526 7001_ $$aRingman, John M.$$b32
000269526 7001_ $$aMendez, Patricio Chrem$$b33
000269526 7001_ $$aSt. George-Hyslop, Peter$$b34
000269526 7001_ $$aFox, Nick C.$$b35
000269526 7001_ $$aSuzuki, Kazushi$$b36
000269526 7001_ $$aOkhravi, Hamid R.$$b37
000269526 7001_ $$aChhatwal, Jasmeer$$b38
000269526 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b39
000269526 7001_ $$0P:(DE-2719)2000010$$aJucker, Mathias$$b40
000269526 7001_ $$aSims, John R.$$b41
000269526 7001_ $$aHoldridge, Karen C.$$b42
000269526 7001_ $$aProctor, Nicholas K.$$b43
000269526 7001_ $$aYaari, Roy$$b44
000269526 7001_ $$aAndersen, Scott W.$$b45
000269526 7001_ $$aMancini, Michele$$b46
000269526 7001_ $$aLlibre-Guerra, Jorge$$b47
000269526 7001_ $$aBateman, Randall J.$$b48
000269526 7001_ $$aMcDade, Eric$$b49
000269526 7001_ $$aDaniels, Alisha J.$$b50
000269526 7001_ $$aCourtney, Laura$$b51
000269526 7001_ $$aXu, Xiong$$b52
000269526 7001_ $$aLu, Ruijin$$b53
000269526 7001_ $$aGremminger, Emily$$b54
000269526 7001_ $$aFranklin, Erin$$b55
000269526 7001_ $$aIbanez, Laura$$b56
000269526 7001_ $$aJerome, Gina$$b57
000269526 7001_ $$aHerries, Elizabeth$$b58
000269526 7001_ $$aStauber, Jennifer$$b59
000269526 7001_ $$aBaker, Bryce$$b60
000269526 7001_ $$aMinton, Matthew$$b61
000269526 7001_ $$aGoate, Alison M.$$b62
000269526 7001_ $$aRenton, Alan E.$$b63
000269526 7001_ $$aPicarello, Danielle M.$$b64
000269526 7001_ $$aHornbeck, Russ$$b65
000269526 7001_ $$aChen, Allison$$b66
000269526 7001_ $$aChen, Charles$$b67
000269526 7001_ $$aFlores, Shaney$$b68
000269526 7001_ $$aJoseph-Mathurin, Nelly$$b69
000269526 7001_ $$aJarman, Steve$$b70
000269526 7001_ $$aJackson, Kelley$$b71
000269526 7001_ $$aKeefe, Sarah$$b72
000269526 7001_ $$aKoudelis, Deborah$$b73
000269526 7001_ $$aMassoumzadeh, Parinaz$$b74
000269526 7001_ $$aMcCullough, Austin$$b75
000269526 7001_ $$aMcKay, Nicole$$b76
000269526 7001_ $$aNicklaus, Joyce$$b77
000269526 7001_ $$aPulizos, Christine$$b78
000269526 7001_ $$0P:(DE-2719)9000806$$aWang, Qing$$b79
000269526 7001_ $$aSabaredzovic, Edita$$b80
000269526 7001_ $$aSmith, Hunter$$b81
000269526 7001_ $$aScott, Jalen$$b82
000269526 7001_ $$aSimmons, Ashlee$$b83
000269526 7001_ $$aRizzo, Jacqueline$$b84
000269526 7001_ $$aSmith, Jennifer$$b85
000269526 7001_ $$aStout, Sarah$$b86
000269526 7001_ $$aKarch, Celeste M.$$b87
000269526 7001_ $$aMarsh, Jacob$$b88
000269526 7001_ $$aHoltzman, David M.$$b89
000269526 7001_ $$aBarthelemy, Nicolas$$b90
000269526 7001_ $$aXu, Jinbin$$b91
000269526 7001_ $$aNoble, James M.$$b92
000269526 7001_ $$aIkonomovic, Snezana$$b93
000269526 7001_ $$aNadkarni, Neelesh K.$$b94
000269526 7001_ $$aGraff-Radford, Neill R.$$b95
000269526 7001_ $$aIkeuchi, Takeshi$$b96
000269526 7001_ $$aKasuga, Kensaku$$b97
000269526 7001_ $$aNiimi, Yoshiki$$b98
000269526 7001_ $$aHuey, Edward D.$$b99
000269526 7001_ $$aSalloway, Stephen$$b100
000269526 7001_ $$aSchofield, Peter R.$$b101
000269526 7001_ $$aBechara, Jacob A.$$b102
000269526 7001_ $$aMartins, Ralph$$b103
000269526 7001_ $$aCash, David M.$$b104
000269526 7001_ $$aRyan, Natalie S.$$b105
000269526 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b106$$udzne
000269526 7001_ $$0P:(DE-2719)2814244$$aHofmann, Anna$$b107$$udzne
000269526 7001_ $$0P:(DE-2719)2810869$$aKuder-Buletta, Elke$$b108$$udzne
000269526 7001_ $$0P:(DE-2719)2810662$$aGräber-Sultan, Susanne$$b109$$udzne
000269526 7001_ $$aObermueller, Ulrike$$b110
000269526 7001_ $$0P:(DE-2719)2810668$$aRödenbeck, Yvonne Esther$$b111$$udzne
000269526 7001_ $$aVӧglein, Jonathan$$b112
000269526 7001_ $$0P:(DE-HGF)0$$aLee, Jae-Hong$$b113
000269526 7001_ $$aRoh, Jee Hoon$$b114
000269526 7001_ $$aSanchez-Valle, Raquel$$b115
000269526 7001_ $$aRosa-Neto, Pedro$$b116
000269526 7001_ $$aAllegri, Ricardo F.$$b117
000269526 7001_ $$aSurace, Ezequiel$$b118
000269526 7001_ $$aVazquez, Silvia$$b119
000269526 7001_ $$aLopera, Francisco$$b120
000269526 7001_ $$aLeon, Yudy Milena$$b121
000269526 7001_ $$aRamirez, Laura$$b122
000269526 7001_ $$aAguillon, David$$b123
000269526 7001_ $$aLevey, Allan I.$$b124
000269526 7001_ $$aJohnson, Erik C. B$$b125
000269526 7001_ $$aSeyfried, Nicholas T.$$b126
000269526 7001_ $$aFagan, Anne M.$$b127
000269526 7001_ $$aMori, Hiroshi$$b128
000269526 7001_ $$aMasters, Colin$$b129
000269526 773__ $$0PERI:(DE-600)2701924-X$$a10.1001/jamaneurol.2024.0991$$n6$$p582 - 593$$tJAMA neurology$$v81$$x2168-6149$$y2024
000269526 8564_ $$uhttps://pub.dzne.de/record/269526/files/DZNE-2024-00567%20SUP1.pdf
000269526 8564_ $$uhttps://pub.dzne.de/record/269526/files/DZNE-2024-00567%20SUP2.pdf
000269526 8564_ $$uhttps://pub.dzne.de/record/269526/files/DZNE-2024-00567%20SUP3.pdf
000269526 8564_ $$uhttps://pub.dzne.de/record/269526/files/DZNE-2024-00567%20SUP1.pdf?subformat=pdfa$$xpdfa
000269526 8564_ $$uhttps://pub.dzne.de/record/269526/files/DZNE-2024-00567%20SUP2.pdf?subformat=pdfa$$xpdfa
000269526 8564_ $$uhttps://pub.dzne.de/record/269526/files/DZNE-2024-00567%20SUP3.pdf?subformat=pdfa$$xpdfa
000269526 8564_ $$uhttps://pub.dzne.de/record/269526/files/DZNE-2024-00567.pdf$$yOpenAccess
000269526 8564_ $$uhttps://pub.dzne.de/record/269526/files/DZNE-2024-00567.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000269526 909CO $$ooai:pub.dzne.de:269526$$pdnbdelivery$$pdriver$$pVDB$$popen_access$$popenaire
000269526 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811659$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b39$$kDZNE
000269526 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2000010$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b40$$kDZNE
000269526 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)9000806$$aExternal Institute$$b79$$kExtern
000269526 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)2000055$$aExternal Institute$$b106$$kExtern
000269526 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)2814244$$aExternal Institute$$b107$$kExtern
000269526 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)2810869$$aExternal Institute$$b108$$kExtern
000269526 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)2810662$$aExternal Institute$$b109$$kExtern
000269526 9101_ $$0I:(DE-HGF)0$$6P:(DE-2719)2810668$$aExternal Institute$$b111$$kExtern
000269526 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
000269526 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
000269526 9141_ $$y2024
000269526 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2023-10-26
000269526 915__ $$0LIC:(DE-HGF)CCBY4$$2HGFVOC$$aCreative Commons Attribution CC BY 4.0
000269526 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJAMA NEUROL : 2022$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000269526 915__ $$0StatID:(DE-HGF)9925$$2StatID$$aIF >= 25$$bJAMA NEUROL : 2022$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2023-10-26
000269526 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-10-26
000269526 9201_ $$0I:(DE-2719)1111016$$kAG Levin$$lClinical Neurodegeneration$$x0
000269526 9201_ $$0I:(DE-2719)1210001$$kAG Jucker$$lCell Biology of Neurological Diseases$$x1
000269526 9201_ $$0I:(DE-2719)1111015$$kClinical Research (Munich)$$lClinical Research (Munich)$$x2
000269526 980__ $$ajournal
000269526 980__ $$aVDB
000269526 980__ $$aI:(DE-2719)1111016
000269526 980__ $$aI:(DE-2719)1210001
000269526 980__ $$aI:(DE-2719)1111015
000269526 980__ $$aUNRESTRICTED
000269526 9801_ $$aFullTexts