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@ARTICLE{Bergstrm:155714,
author = {Bergström, Sofia and Remnestål, Julia and Yousef, Jamil
and Olofsson, Jennie and Markaki, Ioanna and Carvalho,
Stephanie and Corvol, Jean-Christophe and Kultima, Kim and
Kilander, Lena and Löwenmark, Malin and Ingelsson, Martin
and Blennow, Kaj and Zetterberg, Henrik and Nellgård, Bengt
and Brosseron, Frederic and Heneka, Michael and Bosch,
Beatriz and Sanchez-Valle, Raquel and Månberg, Anna and
Svenningsson, Per and Nilsson, Peter},
title = {{M}ulti-cohort profiling reveals elevated {CSF} levels of
brain-enriched proteins in {A}lzheimer's disease.},
journal = {Annals of Clinical and Translational Neurology},
volume = {8},
number = {7},
issn = {2328-9503},
address = {Chichester [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2021-00882},
pages = {1456 - 1470},
year = {2021},
abstract = {Decreased amyloid beta (Aβ) 42 together with increased tau
and phospho-tau in cerebrospinal fluid (CSF) is indicative
of Alzheimer's disease (AD). However, the molecular
pathophysiology underlying the slowly progressive cognitive
decline observed in AD is not fully understood and it is not
known what other CSF biomarkers may be altered in early
disease stages.We utilized an antibody-based suspension bead
array to analyze levels of 216 proteins in CSF from AD
patients, patients with mild cognitive impairment (MCI), and
controls from two independent cohorts collected within the
AETIONOMY consortium. Two additional cohorts from Sweden
were used for biological verification.Six proteins,
amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated
phosphoprotein 21 (ARPP21), growth-associated protein 43
(GAP43), neurofilament medium polypeptide (NEFM), and
synuclein beta (SNCB) were found at increased levels in CSF
from AD patients compared with controls. Next, we used CSF
levels of Aβ42 and tau for the stratification of the MCI
patients and observed increased levels of AMPH, AQP4,
ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal
tau levels compared with controls. Further characterization
revealed strong to moderate correlations between these five
proteins and tau concentrations.In conclusion, we report six
extensively replicated candidate biomarkers with the
potential to reflect disease development. Continued
evaluation of these proteins will determine to what extent
they can aid in the discrimination of MCI patients with and
without an underlying AD etiology, and if they have the
potential to contribute to a better understanding of the AD
continuum.},
keywords = {Adult / Aged / Aged, 80 and over / Alzheimer Disease:
cerebrospinal fluid / Alzheimer Disease: diagnosis / Amyloid
beta-Peptides: cerebrospinal fluid / Aquaporin 4:
cerebrospinal fluid / Biomarkers: cerebrospinal fluid /
Brain: metabolism / Cognitive Dysfunction: cerebrospinal
fluid / Cognitive Dysfunction: diagnosis / Cohort Studies /
Cross-Sectional Studies / Female / GAP-43 Protein:
cerebrospinal fluid / Humans / Male / Middle Aged / Nerve
Tissue Proteins: cerebrospinal fluid / Neurofilament
Proteins: cerebrospinal fluid / Peptide Fragments:
cerebrospinal fluid / Phosphoproteins: cerebrospinal fluid /
Protein Array Analysis: methods / beta-Synuclein:
cerebrospinal fluid / tau Proteins: cerebrospinal fluid},
cin = {Biomarker},
ddc = {610},
cid = {I:(DE-2719)1011301},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34129723},
pmc = {pmc:PMC8283172},
doi = {10.1002/acn3.51402},
url = {https://pub.dzne.de/record/155714},
}