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000140473 0247_ $$2pmc$$apmc:PMC6367005
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000140473 0247_ $$2ISSN$$a1546-170X
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000140473 037__ $$aDZNE-2020-06795
000140473 041__ $$aEnglish
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000140473 1001_ $$0P:(DE-2719)2811828$$aPreische, Oliver$$b0$$eFirst author$$udzne
000140473 245__ $$aSerum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease.
000140473 260__ $$aNew York, NY$$bNature America Inc.$$c2019
000140473 264_1 $$2Crossref$$3online$$bSpringer Science and Business Media LLC$$c2019-01-21
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000140473 520__ $$aNeurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker.
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000140473 542__ $$2Crossref$$i2019-01-21$$uhttp://www.springer.com/tdm
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000140473 650_7 $$2NLM Chemicals$$aNeurofilament Proteins
000140473 650_7 $$2NLM Chemicals$$aneurofilament protein L
000140473 650_2 $$2MeSH$$aAlzheimer Disease: blood
000140473 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000140473 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000140473 650_2 $$2MeSH$$aDisease Progression
000140473 650_2 $$2MeSH$$aHumans
000140473 650_2 $$2MeSH$$aMutation: genetics
000140473 650_2 $$2MeSH$$aNerve Degeneration: blood
000140473 650_2 $$2MeSH$$aNeurofilament Proteins: blood
000140473 650_2 $$2MeSH$$aNeurofilament Proteins: cerebrospinal fluid
000140473 650_2 $$2MeSH$$aNeurofilament Proteins: genetics
000140473 7001_ $$aSchultz, Stephanie A$$b1
000140473 7001_ $$0P:(DE-2719)2812177$$aApel, Anja$$b2$$udzne
000140473 7001_ $$aKuhle, Jens$$b3
000140473 7001_ $$0P:(DE-2719)9000387$$aKaeser, Stephan A$$b4$$udzne
000140473 7001_ $$aBarro, Christian$$b5
000140473 7001_ $$0P:(DE-2719)2810662$$aGräber, Susanne$$b6$$udzne
000140473 7001_ $$0P:(DE-2719)2810869$$aKuder-Buletta, Elke$$b7$$udzne
000140473 7001_ $$0P:(DE-2719)9000177$$ala Fougère, Christian$$b8$$udzne
000140473 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b9$$udzne
000140473 7001_ $$0P:(DE-2719)2811820$$aVöglein, Jonathan$$b10$$udzne
000140473 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b11$$udzne
000140473 7001_ $$aMasters, Colin L$$b12
000140473 7001_ $$aMartins, Ralph$$b13
000140473 7001_ $$aSchofield, Peter R$$b14
000140473 7001_ $$aRossor, Martin N$$b15
000140473 7001_ $$aGraff-Radford, Neill R$$b16
000140473 7001_ $$aSalloway, Stephen$$b17
000140473 7001_ $$aGhetti, Bernardino$$b18
000140473 7001_ $$aRingman, John M$$b19
000140473 7001_ $$aNoble, James M$$b20
000140473 7001_ $$aChhatwal, Jasmeer$$b21
000140473 7001_ $$aGoate, Alison M$$b22
000140473 7001_ $$aBenzinger, Tammie L S$$b23
000140473 7001_ $$aMorris, John C$$b24
000140473 7001_ $$aBateman, Randall J$$b25
000140473 7001_ $$aWang, Guoqiao$$b26
000140473 7001_ $$aFagan, Anne M$$b27
000140473 7001_ $$aMcDade, Eric M$$b28
000140473 7001_ $$aGordon, Brian A$$b29
000140473 7001_ $$0P:(DE-2719)2000010$$aJucker, Mathias$$b30$$eCorresponding author$$udzne
000140473 7001_ $$aNetwork, Dominantly Inherited Alzheimer$$b31
000140473 7001_ $$aAllegri, Ricardo$$b32
000140473 7001_ $$aAmtashar, Fatima$$b33
000140473 7001_ $$aBateman, Randall$$b34
000140473 7001_ $$aBenzinger, Tammie$$b35
000140473 7001_ $$aBerman, Sarah$$b36
000140473 7001_ $$aBodge, Courtney$$b37
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000140473 7001_ $$aBrooks, William$$b39
000140473 7001_ $$aBuck, Jill$$b40
000140473 7001_ $$aBuckles, Virginia$$b41
000140473 7001_ $$aChea, Sochenda$$b42
000140473 7001_ $$aChhatwal, Jasmeer$$b43
000140473 7001_ $$aChrem, Patricio$$b44
000140473 7001_ $$aChui, Helena$$b45
000140473 7001_ $$aCinco, Jake$$b46
000140473 7001_ $$aClifford, Jack$$b47
000140473 7001_ $$aCruchaga, Carlos$$b48
000140473 7001_ $$aD'Mello, Mirelle$$b49
000140473 7001_ $$aDonahue, Tamara$$b50
000140473 7001_ $$aDouglas, Jane$$b51
000140473 7001_ $$aEdigo, Noelia$$b52
000140473 7001_ $$aErekin-Taner, Nilufer$$b53
000140473 7001_ $$aFagan, Anne$$b54
000140473 7001_ $$aFarlow, Marty$$b55
000140473 7001_ $$aFarrar, Angela$$b56
000140473 7001_ $$aFeldman, Howard$$b57
000140473 7001_ $$aFlynn, Gigi$$b58
000140473 7001_ $$aFox, Nick$$b59
000140473 7001_ $$aFranklin, Erin$$b60
000140473 7001_ $$aFujii, Hisako$$b61
000140473 7001_ $$aGant, Cortaiga$$b62
000140473 7001_ $$aGardener, Samantha$$b63
000140473 7001_ $$aGhetti, Bernardino$$b64
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000140473 7001_ $$aGoldman, Jill$$b66
000140473 7001_ $$aGordon, Brian$$b67
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000140473 7001_ $$aGray, Julia$$b69
000140473 7001_ $$aGurney, Jenny$$b70
000140473 7001_ $$aHassenstab, Jason$$b71
000140473 7001_ $$aHirohara, Mie$$b72
000140473 7001_ $$aHoltzman, David$$b73
000140473 7001_ $$aHornbeck, Russ$$b74
000140473 7001_ $$0P:(DE-2719)9000054$$aDiBari, Siri Houeland$$b75$$udzne
000140473 7001_ $$aIkeuchi, Takeshi$$b76
000140473 7001_ $$aIkonomovic, Snezana$$b77
000140473 7001_ $$aJerome, Gina$$b78
000140473 7001_ $$aKarch, Celeste$$b79
000140473 7001_ $$aKasuga, Kensaku$$b80
000140473 7001_ $$aKawarabayashi, Takeshi$$b81
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000140473 7001_ $$aMaue-Dreyfus, Denise$$b90
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000140473 7001_ $$aMontoya, Lucy$$b92
000140473 7001_ $$aMori, Hiroshi$$b93
000140473 7001_ $$aMorris, John$$b94
000140473 7001_ $$aNagamatsu, Akem$$b95
000140473 7001_ $$aNeimeyer, Katie$$b96
000140473 7001_ $$aNoble, James$$b97
000140473 7001_ $$aNorton, Joanne$$b98
000140473 7001_ $$aPerrin, Richard$$b99
000140473 7001_ $$aRaichle, Marc$$b100
000140473 7001_ $$aRingman, John$$b101
000140473 7001_ $$aRoh, Jee Hoon$$b102
000140473 7001_ $$aSalloway, Stephen$$b103
000140473 7001_ $$aSchofield, Peter$$b104
000140473 7001_ $$aShimada, Hiroyuki$$b105
000140473 7001_ $$aShiroto, Tomoyo$$b106
000140473 7001_ $$aShoji, Mikio$$b107
000140473 7001_ $$aSigurdson, Wendy$$b108
000140473 7001_ $$aSohrabi, Hamid$$b109
000140473 7001_ $$aSparks, Paige$$b110
000140473 7001_ $$aSuzuki, Kazushi$$b111
000140473 7001_ $$aSwisher, Laura$$b112
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000140473 7001_ $$aWeiner, Mike$$b116
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000140473 77318 $$2Crossref$$3journal-article$$a10.1038/s41591-018-0304-3$$b : Springer Science and Business Media LLC, 2019-01-21$$n2$$p277-283$$tNature Medicine$$v25$$x1078-8956$$y2019
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000140473 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367005
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