TY  - JOUR
AU  - Bergström, Sofia
AU  - Remnestål, Julia
AU  - Yousef, Jamil
AU  - Olofsson, Jennie
AU  - Markaki, Ioanna
AU  - Carvalho, Stephanie
AU  - Corvol, Jean-Christophe
AU  - Kultima, Kim
AU  - Kilander, Lena
AU  - Löwenmark, Malin
AU  - Ingelsson, Martin
AU  - Blennow, Kaj
AU  - Zetterberg, Henrik
AU  - Nellgård, Bengt
AU  - Brosseron, Frederic
AU  - Heneka, Michael
AU  - Bosch, Beatriz
AU  - Sanchez-Valle, Raquel
AU  - Månberg, Anna
AU  - Svenningsson, Per
AU  - Nilsson, Peter
TI  - Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease.
JO  - Annals of Clinical and Translational Neurology
VL  - 8
IS  - 7
SN  - 2328-9503
CY  - Chichester [u.a.]
PB  - Wiley
M1  - DZNE-2021-00882
SP  - 1456 - 1470
PY  - 2021
AB  - 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.
KW  - Adult
KW  - Aged
KW  - Aged, 80 and over
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Alzheimer Disease: diagnosis
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Aquaporin 4: cerebrospinal fluid
KW  - Biomarkers: cerebrospinal fluid
KW  - Brain: metabolism
KW  - Cognitive Dysfunction: cerebrospinal fluid
KW  - Cognitive Dysfunction: diagnosis
KW  - Cohort Studies
KW  - Cross-Sectional Studies
KW  - Female
KW  - GAP-43 Protein: cerebrospinal fluid
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Nerve Tissue Proteins: cerebrospinal fluid
KW  - Neurofilament Proteins: cerebrospinal fluid
KW  - Peptide Fragments: cerebrospinal fluid
KW  - Phosphoproteins: cerebrospinal fluid
KW  - Protein Array Analysis: methods
KW  - beta-Synuclein: cerebrospinal fluid
KW  - tau Proteins: cerebrospinal fluid
LB  - PUB:(DE-HGF)16
C6  - pmid:34129723
C2  - pmc:PMC8283172
DO  - DOI:10.1002/acn3.51402
UR  - https://pub.dzne.de/record/155714
ER  -