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@ARTICLE{Hofmann:272980,
author = {Hofmann, Anna and Häsler, Lisa M and Lambert, Marius and
Kaeser, Stephan and Gräber-Sultan, Susanne and Obermüller,
Ulrike and Kuder-Buletta, Elke and la Fougère, Christian
and Laske, Christoph and Vöglein, Jonathan and Levin,
Johannes and Fox, Nick C and Ryan, Natalie S and Zetterberg,
Henrik and Llibre-Guerra, Jorge J and Perrin, Richard J and
Ibanez, Laura and Schofield, Peter R and Brooks, William S
and Day, Gregory S and Farlow, Martin R and Allegri, Ricardo
F and Chrem Mendez, Patricio and Ikeuchi, Takeshi and
Kasuga, Kensaku and Lee, Jae-Hong and Roh, Jee Hoon and
Mori, Hiroshi and Lopera, Francisco and Bateman, Randall J
and McDade, Eric and Gordon, Brian A and Chhatwal, Jasmeer P
and Jucker, Mathias and Schultz, Stephanie A},
collaboration = {Network, Dominantly Inherited Alzheimer},
othercontributors = {Aguillon, David and Aschenbrenner, Andrew J and Baker,
Bryce and Barthelemy, Nicolas and Bateman, Randall and
Bechara, Jacob A and Benzinger, Tammie and Berman, Sarah B
and Cash, David M and Chen, Allison and Chen, Charles and
Chhatwal Chhatwal, Jasmeer P and Mendez, Patricio Chrem and
Courtney, Laura and Cruchaga, Carlos and Daniels, Alisha J
and Day, Gregory S and Fagan, Anne M and Farlow, Martin and
Flores, Shaney and Franklin, Erin and Goate, Alison M and
Gräber-Sultan, Susanne and Graff-Radford, Neill R and
Gremminger, Emily and Hassenstab, Jason and Herries,
Elizabeth and Holtzman, David M and Hornbeck, Russ and Huey,
Edward D and Ikonomovic, Snezana and Jackson, Kelley and
Jarman, Steve and Jerome, Gina and Johnson, Erik C B and
Joseph-Mathurin, Nelly and Karch, Celeste M and Keefe, Sarah
and Koudelis, Deborah and Laske, Christoph and Leon, Yudy
Milena and Levey, Allan I and Li, Yan and Lu, Ruijin and
Marsh, Jacob and Martins, Ralph and Massoumzadeh, Parinaz
and Masters, Colin and McCullough, Austin and McDade, Eric
and McKay, Nicole and Minton, Matthew and Morris, John C and
Nadkarni, Neelesh K and Nicklaus, Joyce and Niimi, Yoshiki
and Noble, James M and Obermueller, Ulrike and Picarello,
Danielle M and Pulizos, Christine and Ramirez, Laura and
Renton, Alan E and Ringman, John and Rizzo, Jacqueline and
Rödenbeck, Yvonne Esther and Rosa-Neto, Pedro and
Sabaredzovic, Edita and Salloway, Stephen and Sanchez-Valle,
Raquel and Scott, Jalen and Seyfried, Nicholas T and
Simmons, Ashlee and Smith, Jennifer and Smith, Hunter and
Stauber, Jennifer and Stout, Sarah and Supnet-Bell, Charlene
and Surace, Ezequiel and Vazquez, Silvia and Vöglein,
Jonathan and Wang, Guoqiao and Wang, Qing and Xiong, Chengie
and Xu, Xiong and Xu, Jinbin},
title = {{C}omparative neurofilament light chain trajectories in
{CSF} and plasma in autosomal dominant {A}lzheimer's
disease.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2024-01359},
pages = {9982},
year = {2024},
abstract = {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.},
keywords = {Humans / Alzheimer Disease: cerebrospinal fluid / Alzheimer
Disease: blood / Alzheimer Disease: genetics / Alzheimer
Disease: diagnosis / Neurofilament Proteins: blood /
Neurofilament Proteins: cerebrospinal fluid / Male / Female
/ Biomarkers: cerebrospinal fluid / Biomarkers: blood /
Middle Aged / Cross-Sectional Studies / Adult / Longitudinal
Studies / Amyloid beta-Peptides: cerebrospinal fluid /
Amyloid beta-Peptides: blood / Atrophy / Gray Matter:
pathology / Gray Matter: diagnostic imaging / Aged /
Positron-Emission Tomography / Disease Progression /
Neurofilament Proteins (NLM Chemicals) / Biomarkers (NLM
Chemicals) / neurofilament protein L (NLM Chemicals) /
Amyloid beta-Peptides (NLM Chemicals)},
cin = {AG Jucker / AG Gasser / Clinical Research (Munich)},
ddc = {500},
cid = {I:(DE-2719)1210001 / I:(DE-2719)1210000 /
I:(DE-2719)1111015},
pnm = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
experiment = {EXP:(DE-2719)DIAN-20090101},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11574007},
pubmed = {pmid:39557867},
doi = {10.1038/s41467-024-52937-8},
url = {https://pub.dzne.de/record/272980},
}