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@ARTICLE{Johnson:259941,
author = {Johnson, Erik C B and Bian, Shijia and Haque, Rafi U and
Carter, E Kathleen and Watson, Caroline M and Gordon, Brian
A and Ping, Lingyan and Duong, Duc M and Epstein, Michael P
and McDade, Eric and Barthélemy, Nicolas R and Karch,
Celeste M and Xiong, Chengjie and Cruchaga, Carlos and
Perrin, Richard J and Wingo, Aliza P and Wingo, Thomas S and
Chhatwal, Jasmeer P and Day, Gregory S and Noble, James M
and Berman, Sarah B and Martins, Ralph and Graff-Radford,
Neill R and Schofield, Peter R and Ikeuchi, Takeshi and
Mori, Hiroshi and Levin, Johannes and Farlow, Martin and
Lah, James J and Haass, Christian and Jucker, Mathias and
Morris, John C and Benzinger, Tammie L S and Roberts, Blaine
R and Bateman, Randall J and Fagan, Anne M and Seyfried,
Nicholas T and Levey, Allan I},
collaboration = {Network, Dominantly Inherited Alzheimer},
othercontributors = {Noble, James M and Day, Gregory S and Graff-Radford, Neill
R and Voglein, Jonathan and Allegri, Ricardo and Mendez,
Patricio Chrem and Surace, Ezequiel and Berman, Sarah B and
Ikonomovic, Snezana and Nadkarni, Neelesh and Lopera,
Francisco and Ramirez, Laura and Aguillon, David and Leon,
Yudy and Ramos, Claudia and Alzate, Diana and Baena, Ana and
Londono, Natalia and Moreno, Sonia and Laske, Christoph and
Kuder-Buletta, Elke and Graber-Sultan, Susanne and Preische,
Oliver and Hofmann, Anna and Ikeuchi, Takeshi and Kasuga,
Kensaku and Niimi, Yoshiki and Ishii, Kenji and Senda,
Michio and Sanchez-Valle, Raquel and Rosa-Neto, Pedro and
Fox, Nick and Cash, Dave and Lee, Jae-Hong and Roh, Jee Hoon
and Riddle, Meghan and Menard, William and Bodge, Courtney
and Surti, Mustafa and Takada, Leonel Tadao and Chhatwal,
Jasmeer P and Sanchez-Gonzalez, V. J. and Orozco-Barajas,
Maribel and Goate, Alison and Renton, Alan and Esposito,
Bianca and Karch, Celeste M and Marsh, Jacob and Cruchaga,
Carlos and Fernandez, Victoria and Gordon, Brian A and
Fagan, Anne M and Jerome, Gina and Herries, Elizabeth and
Llibre-Guerra, Jorge and Johnson, Erik C B and Seyfried,
Nicholas T and Schofield, Peter R and Brooks, William and
Bechara, Jacob and Bateman, Randall J and Hassenstab, Jason
and Perrin, Richard J and Franklin, Erin and Benzinger,
Tammie L S and Chen, Allison and Chen, Charles and Flores,
Shaney and Friedrichsen, Nelly and Hantler, Nancy and
Hornbeck, Russ and Jarman, Steve and Keefe, Sarah and
Koudelis, Deborah and Massoumzadeh, Parinaz and McCullough,
Austin and McKay, Nicole and Nicklaus, Joyce and Pulizos,
Christine and Wang, Qing and Mishall, Sheetal and
Sabaredzovic, Edita and Deng, Emily and Candela, Madison and
Smith, Hunter and Hobbs, Diana and Scott, Jalen and Levin,
Johannes and Xiong, Chengjie and Wang, Peter and Xu, Xiong
and Li, Yan and Gremminger, Emily and Ma, Yinjiao and Bui,
Ryan and Lu, Ruijin and Ortiz, Ana Luisa Sosa and Daniels,
Alisha and Courtney, Laura and Supnet-Bell, Charlene and Xu,
Jinbin and Ringman, John},
title = {{C}erebrospinal fluid proteomics define the natural history
of autosomal dominant {A}lzheimer's disease.},
journal = {Nature medicine},
volume = {29},
number = {8},
issn = {1078-8956},
address = {New York, NY},
publisher = {Nature America Inc.},
reportid = {DZNE-2023-00805},
pages = {1979 - 1988},
year = {2023},
abstract = {Alzheimer's disease (AD) pathology develops many years
before the onset of cognitive symptoms. Two pathological
processes-aggregation of the amyloid-β (Aβ) peptide into
plaques and the microtubule protein tau into neurofibrillary
tangles (NFTs)-are hallmarks of the disease. However, other
pathological brain processes are thought to be key disease
mediators of Aβ plaque and NFT pathology. How these
additional pathologies evolve over the course of the disease
is currently unknown. Here we show that proteomic
measurements in autosomal dominant AD cerebrospinal fluid
(CSF) linked to brain protein coexpression can be used to
characterize the evolution of AD pathology over a timescale
spanning six decades. SMOC1 and SPON1 proteins associated
with Aβ plaques were elevated in AD CSF nearly 30 years
before the onset of symptoms, followed by changes in
synaptic proteins, metabolic proteins, axonal proteins,
inflammatory proteins and finally decreases in
neurosecretory proteins. The proteome discriminated mutation
carriers from noncarriers before symptom onset as well or
better than Aβ and tau measures. Our results highlight the
multifaceted landscape of AD pathophysiology and its
temporal evolution. Such knowledge will be critical for
developing precision therapeutic interventions and
biomarkers for AD beyond those associated with Aβ and tau.},
keywords = {Alzheimer Disease: cerebrospinal fluid / Humans / Alzheimer
Disease: pathology / Proteomics / Amyloid beta-Peptides:
metabolism / tau Proteins: metabolism / Neurofibrillary
Tangles: pathology / Biomarkers: metabolism / Alzheimer
Disease: genetics / Alzheimer Disease: physiopathology /
Male / Female / Adult / Middle Aged / Mutation / Age of
Onset / SMOC1 protein, human (NLM Chemicals) / Amyloid
beta-Peptides (NLM Chemicals) / tau Proteins (NLM Chemicals)
/ Biomarkers (NLM Chemicals)},
cin = {AG Haass / AG Jucker},
ddc = {610},
cid = {I:(DE-2719)1110007 / I:(DE-2719)1210001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
experiment = {EXP:(DE-2719)DIAN-20090101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37550416},
pmc = {pmc:PMC10427428},
doi = {10.1038/s41591-023-02476-4},
url = {https://pub.dzne.de/record/259941},
}