Journal Article

DZNE-2021-00882

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease.

Bergström, S. ; Remnestål, J. ; Yousef, J. ; Olofsson, J. ; Markaki, I. ; Carvalho, S. ; Corvol, J.-C. ; Kultima, K. ; Kilander, L. ; Löwenmark, M. ; Ingelsson, M. ; Blennow, K. ; Zetterberg, H. ; Nellgård, B. ; Brosseron, F.DZNE* ; Heneka, M.Extern* ; Bosch, B. ; Sanchez-Valle, R. ; Månberg, A. ; Svenningsson, P. ; Nilsson, P.

2021
Wiley Chichester [u.a.]

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Please use a persistent id in citations: doi:10.1002/acn3.51402

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.

Keyword(s): Adult (MeSH) ; Aged (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; Alzheimer Disease: diagnosis (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Aquaporin 4: cerebrospinal fluid (MeSH) ; Biomarkers: cerebrospinal fluid (MeSH) ; Brain: metabolism (MeSH) ; Cognitive Dysfunction: cerebrospinal fluid (MeSH) ; Cognitive Dysfunction: diagnosis (MeSH) ; Cohort Studies (MeSH) ; Cross-Sectional Studies (MeSH) ; Female (MeSH) ; GAP-43 Protein: cerebrospinal fluid (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Nerve Tissue Proteins: cerebrospinal fluid (MeSH) ; Neurofilament Proteins: cerebrospinal fluid (MeSH) ; Peptide Fragments: cerebrospinal fluid (MeSH) ; Phosphoproteins: cerebrospinal fluid (MeSH) ; Protein Array Analysis: methods (MeSH) ; beta-Synuclein: cerebrospinal fluid (MeSH) ; tau Proteins: cerebrospinal fluid (MeSH)

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Contributing Institute(s):

1. Interventional Trials and Biomarkers in Neurodegenerative Diseases (Biomarker)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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