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000272980 1001_ $$0P:(DE-2719)2814244$$aHofmann, Anna$$b0$$eFirst author$$udzne
000272980 245__ $$aComparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease.
000272980 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000272980 520__ $$aDisease-modifying therapies for Alzheimer's disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum. CSF and plasma trajectories were similar at presymptomatic stages, discriminating mutation carriers from non-carrier controls 10-20 years before the estimated onset of clinical symptoms, depending on the statistical model used. However, after symptom onset the rate of change in CSF NfL continued to increase steadily, whereas the rate of change in plasma NfL leveled off. Both plasma and CSF NfL changes were associated with grey-matter atrophy, but not with Aβ-PET changes, supporting a temporal decoupling of Aβ deposition and neurodegeneration. These observations support NfL in both CSF and blood as an early marker of neurodegeneration but suggest that NfL measured in the CSF may be better suited for monitoring clinical trial outcomes in symptomatic AD patients.
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000272980 650_7 $$2NLM Chemicals$$aNeurofilament Proteins
000272980 650_7 $$2NLM Chemicals$$aBiomarkers
000272980 650_7 $$2NLM Chemicals$$aneurofilament protein L
000272980 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000272980 650_2 $$2MeSH$$aHumans
000272980 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000272980 650_2 $$2MeSH$$aAlzheimer Disease: blood
000272980 650_2 $$2MeSH$$aAlzheimer Disease: genetics
000272980 650_2 $$2MeSH$$aAlzheimer Disease: diagnosis
000272980 650_2 $$2MeSH$$aNeurofilament Proteins: blood
000272980 650_2 $$2MeSH$$aNeurofilament Proteins: cerebrospinal fluid
000272980 650_2 $$2MeSH$$aMale
000272980 650_2 $$2MeSH$$aFemale
000272980 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000272980 650_2 $$2MeSH$$aBiomarkers: blood
000272980 650_2 $$2MeSH$$aMiddle Aged
000272980 650_2 $$2MeSH$$aCross-Sectional Studies
000272980 650_2 $$2MeSH$$aAdult
000272980 650_2 $$2MeSH$$aLongitudinal Studies
000272980 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000272980 650_2 $$2MeSH$$aAmyloid beta-Peptides: blood
000272980 650_2 $$2MeSH$$aAtrophy
000272980 650_2 $$2MeSH$$aGray Matter: pathology
000272980 650_2 $$2MeSH$$aGray Matter: diagnostic imaging
000272980 650_2 $$2MeSH$$aAged
000272980 650_2 $$2MeSH$$aPositron-Emission Tomography
000272980 650_2 $$2MeSH$$aDisease Progression
000272980 693__ $$0EXP:(DE-2719)DIAN-20090101$$5EXP:(DE-2719)DIAN-20090101$$eLongitudinal Study on Dominantly Inherited Alzheimer's Disease$$x0
000272980 7001_ $$0P:(DE-2719)2811581$$aHäsler, Lisa M$$b1$$udzne
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000272980 7001_ $$0P:(DE-2719)9000387$$aKaeser, Stephan$$b3$$udzne
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000272980 7001_ $$0P:(DE-2719)2814201$$aObermüller, Ulrike$$b5$$udzne
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000272980 7001_ $$0P:(DE-2719)9000177$$ala Fougère, Christian$$b7
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000272980 7001_ $$0P:(DE-2719)2811820$$aVöglein, Jonathan$$b9
000272980 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b10
000272980 7001_ $$00000-0002-6660-657X$$aFox, Nick C$$b11
000272980 7001_ $$aRyan, Natalie S$$b12
000272980 7001_ $$00000-0003-3930-4354$$aZetterberg, Henrik$$b13
000272980 7001_ $$00000-0002-2137-7750$$aLlibre-Guerra, Jorge J$$b14
000272980 7001_ $$00000-0002-3443-7716$$aPerrin, Richard J$$b15
000272980 7001_ $$aIbanez, Laura$$b16
000272980 7001_ $$00000-0003-2967-9662$$aSchofield, Peter R$$b17
000272980 7001_ $$00000-0001-8603-4233$$aBrooks, William S$$b18
000272980 7001_ $$00000-0001-5133-5538$$aDay, Gregory S$$b19
000272980 7001_ $$00000-0001-7897-5471$$aFarlow, Martin R$$b20
000272980 7001_ $$00000-0001-7166-1234$$aAllegri, Ricardo F$$b21
000272980 7001_ $$aChrem Mendez, Patricio$$b22
000272980 7001_ $$00000-0001-8828-8085$$aIkeuchi, Takeshi$$b23
000272980 7001_ $$00000-0002-2178-0769$$aKasuga, Kensaku$$b24
000272980 7001_ $$0P:(DE-HGF)0$$aLee, Jae-Hong$$b25
000272980 7001_ $$00000-0002-3243-0529$$aRoh, Jee Hoon$$b26
000272980 7001_ $$aMori, Hiroshi$$b27
000272980 7001_ $$00000-0003-3986-1484$$aLopera, Francisco$$b28
000272980 7001_ $$00000-0002-7729-1702$$aBateman, Randall J$$b29
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000272980 7001_ $$00000-0003-2109-2955$$aGordon, Brian A$$b31
000272980 7001_ $$00000-0002-7792-1698$$aChhatwal, Jasmeer P$$b32
000272980 7001_ $$0P:(DE-2719)2000010$$aJucker, Mathias$$b33
000272980 7001_ $$00000-0001-8460-4415$$aSchultz, Stephanie A$$b34
000272980 7001_ $$aNetwork, Dominantly Inherited Alzheimer$$b35$$eCollaboration Author
000272980 7001_ $$aAguillon, David$$b36$$eContributor
000272980 7001_ $$aAschenbrenner, Andrew J$$b37$$eContributor
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000272980 7001_ $$aChen, Allison$$b45$$eContributor
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000272980 7001_ $$aChhatwal Chhatwal, Jasmeer P$$b47$$eContributor
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000272980 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-52937-8$$gVol. 15, no. 1, p. 9982$$n1$$p9982$$tNature Communications$$v15$$x2041-1723$$y2024
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