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| 001 | 272980 | ||
| 005 | 20250127091414.0 | ||
| 024 | 7 | _ | |a pmc:PMC11574007 |2 pmc |
| 024 | 7 | _ | |a 10.1038/s41467-024-52937-8 |2 doi |
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| 024 | 7 | _ | |a altmetric:170637821 |2 altmetric |
| 037 | _ | _ | |a DZNE-2024-01359 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Hofmann, Anna |0 P:(DE-2719)2814244 |b 0 |e First author |u dzne |
| 245 | _ | _ | |a Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease. |
| 260 | _ | _ | |a [London] |c 2024 |b Nature Publishing Group UK |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1733132139_30589 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Disease-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. |
| 536 | _ | _ | |a 352 - Disease Mechanisms (POF4-352) |0 G:(DE-HGF)POF4-352 |c POF4-352 |f POF IV |x 0 |
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| 650 | _ | 7 | |a Neurofilament Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Biomarkers |2 NLM Chemicals |
| 650 | _ | 7 | |a neurofilament protein L |2 NLM Chemicals |
| 650 | _ | 7 | |a Amyloid beta-Peptides |2 NLM Chemicals |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Alzheimer Disease: cerebrospinal fluid |2 MeSH |
| 650 | _ | 2 | |a Alzheimer Disease: blood |2 MeSH |
| 650 | _ | 2 | |a Alzheimer Disease: genetics |2 MeSH |
| 650 | _ | 2 | |a Alzheimer Disease: diagnosis |2 MeSH |
| 650 | _ | 2 | |a Neurofilament Proteins: blood |2 MeSH |
| 650 | _ | 2 | |a Neurofilament Proteins: cerebrospinal fluid |2 MeSH |
| 650 | _ | 2 | |a Male |2 MeSH |
| 650 | _ | 2 | |a Female |2 MeSH |
| 650 | _ | 2 | |a Biomarkers: cerebrospinal fluid |2 MeSH |
| 650 | _ | 2 | |a Biomarkers: blood |2 MeSH |
| 650 | _ | 2 | |a Middle Aged |2 MeSH |
| 650 | _ | 2 | |a Cross-Sectional Studies |2 MeSH |
| 650 | _ | 2 | |a Adult |2 MeSH |
| 650 | _ | 2 | |a Longitudinal Studies |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides: cerebrospinal fluid |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides: blood |2 MeSH |
| 650 | _ | 2 | |a Atrophy |2 MeSH |
| 650 | _ | 2 | |a Gray Matter: pathology |2 MeSH |
| 650 | _ | 2 | |a Gray Matter: diagnostic imaging |2 MeSH |
| 650 | _ | 2 | |a Aged |2 MeSH |
| 650 | _ | 2 | |a Positron-Emission Tomography |2 MeSH |
| 650 | _ | 2 | |a Disease Progression |2 MeSH |
| 693 | _ | _ | |0 EXP:(DE-2719)DIAN-20090101 |5 EXP:(DE-2719)DIAN-20090101 |e Longitudinal Study on Dominantly Inherited Alzheimer's Disease |x 0 |
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| 700 | 1 | _ | |a Perrin, Richard J |0 0000-0002-3443-7716 |b 15 |
| 700 | 1 | _ | |a Ibanez, Laura |b 16 |
| 700 | 1 | _ | |a Schofield, Peter R |0 0000-0003-2967-9662 |b 17 |
| 700 | 1 | _ | |a Brooks, William S |0 0000-0001-8603-4233 |b 18 |
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| 700 | 1 | _ | |a Chrem Mendez, Patricio |b 22 |
| 700 | 1 | _ | |a Ikeuchi, Takeshi |0 0000-0001-8828-8085 |b 23 |
| 700 | 1 | _ | |a Kasuga, Kensaku |0 0000-0002-2178-0769 |b 24 |
| 700 | 1 | _ | |a Lee, Jae-Hong |0 P:(DE-HGF)0 |b 25 |
| 700 | 1 | _ | |a Roh, Jee Hoon |0 0000-0002-3243-0529 |b 26 |
| 700 | 1 | _ | |a Mori, Hiroshi |b 27 |
| 700 | 1 | _ | |a Lopera, Francisco |0 0000-0003-3986-1484 |b 28 |
| 700 | 1 | _ | |a Bateman, Randall J |0 0000-0002-7729-1702 |b 29 |
| 700 | 1 | _ | |a McDade, Eric |b 30 |
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| 700 | 1 | _ | |a Schultz, Stephanie A |0 0000-0001-8460-4415 |b 34 |
| 700 | 1 | _ | |a Network, Dominantly Inherited Alzheimer |b 35 |e Collaboration Author |
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