TY  - JOUR
AU  - Hofmann, Anna
AU  - Häsler, Lisa M
AU  - Lambert, Marius
AU  - Kaeser, Stephan
AU  - Gräber-Sultan, Susanne
AU  - Obermüller, Ulrike
AU  - Kuder-Buletta, Elke
AU  - la Fougère, Christian
AU  - Laske, Christoph
AU  - Vöglein, Jonathan
AU  - Levin, Johannes
AU  - Fox, Nick C
AU  - Ryan, Natalie S
AU  - Zetterberg, Henrik
AU  - Llibre-Guerra, Jorge J
AU  - Perrin, Richard J
AU  - Ibanez, Laura
AU  - Schofield, Peter R
AU  - Brooks, William S
AU  - Day, Gregory S
AU  - Farlow, Martin R
AU  - Allegri, Ricardo F
AU  - Chrem Mendez, Patricio
AU  - Ikeuchi, Takeshi
AU  - Kasuga, Kensaku
AU  - Lee, Jae-Hong
AU  - Roh, Jee Hoon
AU  - Mori, Hiroshi
AU  - Lopera, Francisco
AU  - Bateman, Randall J
AU  - McDade, Eric
AU  - Gordon, Brian A
AU  - Chhatwal, Jasmeer P
AU  - Jucker, Mathias
AU  - Schultz, Stephanie A
TI  - Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2024-01359
SP  - 9982
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Alzheimer Disease: blood
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: diagnosis
KW  - Neurofilament Proteins: blood
KW  - Neurofilament Proteins: cerebrospinal fluid
KW  - Male
KW  - Female
KW  - Biomarkers: cerebrospinal fluid
KW  - Biomarkers: blood
KW  - Middle Aged
KW  - Cross-Sectional Studies
KW  - Adult
KW  - Longitudinal Studies
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Amyloid beta-Peptides: blood
KW  - Atrophy
KW  - Gray Matter: pathology
KW  - Gray Matter: diagnostic imaging
KW  - Aged
KW  - Positron-Emission Tomography
KW  - Disease Progression
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11574007
C6  - pmid:39557867
DO  - DOI:10.1038/s41467-024-52937-8
UR  - https://pub.dzne.de/record/272980
ER  -