Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease

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Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease

Bergström, Sofia (author): KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik,Division of Affinity Proteomics Department of Protein Science SciLifeLab KTH Royal Institute of Technology Stockholm Sweden

Remnestål, Julia (author): KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab,Division of Affinity Proteomics Department of Protein Science SciLifeLab KTH Royal Institute of Technology Stockholm Sweden

Yousef, Jamil (author): KTH,Affinitets-proteomik,Science for Life Laboratory, SciLifeLab,Division of Affinity Proteomics Department of Protein Science SciLifeLab KTH Royal Institute of Technology Stockholm Sweden

Olofsson, Jennie (author): KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik,Division of Affinity Proteomics Department of Protein Science SciLifeLab KTH Royal Institute of Technology Stockholm Sweden

Markaki, I. (author): Karolinska Institutet,Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden

Carvalho, S. (author): Sorbonne Université Institut du Cerveau ‐ Paris Brain Institute ‐ ICM, Assistance‐Publique Hôpitaux de Paris INSERM CNRS Hôpital Pitié‐Salpêtrière Department of Neurology Centre d’Investigation Clinique Neurosciences Paris France

Corvol, J. C. (author): Sorbonne Université Institut du Cerveau ‐ Paris Brain Institute ‐ ICM, Assistance‐Publique Hôpitaux de Paris INSERM CNRS Hôpital Pitié‐Salpêtrière Department of Neurology Centre d’Investigation Clinique Neurosciences Paris France

Kultima, Kim (author): Uppsala universitet,Klinisk kemi,Institutionen för farmaceutisk biovetenskap,Cancerfarmakologi och beräkningsmedicin

Kilander, Lena (author): Uppsala universitet,Geriatrik

Löwenmark, Malin, 1969- (author): Uppsala universitet,Geriatrik

Ingelsson, Martin (author): Uppsala universitet,Geriatrik

Blennow, Kaj, 1958 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg;Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden

Zetterberg, Henrik, 1973 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology,Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg;Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden;Department of Neurodegenerative Disease UCL Institute of Neurology London UK;UK Dementia Research Institute at UCL London UK

Nellgård, Bengt, 1956 (author): Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för anestesiologi och intensivvård,Institute of Clinical Sciences, Department of Anesthesiology and Intensive care,Anesthesiology and Intensive Care Medicine Sahlgrenska University Hospital Mölndal Sweden;Department of Anesthesiology and Intensive Care Medicine Institute of Clinical Sciences The Sahlgrenska Academy University of Gothenburg

Brosseron, F. (author): Universitätsklinikum Bonn Germany;German Center for Neurodegenerative Diseases (DZNE) Bonn Germany

Heneka, M. T. (author): Universitätsklinikum Bonn Germany

Bosch, B. (author): Alzheimer’s and other cognitive disorders Unit. Service of Neurology Hospital Clínic de Barcelona Institut d'Investigació Biomèdica August Pi i Sunyer University of Barcelona Barcelona Spain

Sanchez-Valle, R. (author): Alzheimer’s and other cognitive disorders Unit. Service of Neurology Hospital Clínic de Barcelona Institut d'Investigació Biomèdica August Pi i Sunyer University of Barcelona Barcelona Spain

Månberg, Anna, 1985- (author): KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik,Division of Affinity Proteomics Department of Protein Science SciLifeLab KTH Royal Institute of Technology Stockholm Sweden

Svenningsson, P. (author): Karolinska Institutet,Department of Clinical Neuroscience Karolinska Institutet Stockholm Sweden

Nilsson, Peter (author): KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik,Division of Affinity Proteomics Department of Protein Science SciLifeLab KTH Royal Institute of Technology Stockholm Sweden

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2021-06-15
2021
English.
In: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:7, s. 1456-1470

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Journal article (peer-reviewed)

Abstract Subject headings

Objective: Decreased amyloid beta (A beta) 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. Methods: 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. Results: 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 A beta 42 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. Interpretation: 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

serum neurofilament light
mild cognitive impairment
cerebrospinal-fluid
plasma biomarkers
pathology
neurodegeneration
amphiphysin
association
determinant
proteomics
Neurosciences & Neurology
Alzheimers disease
Bioteknologi

Publication and Content Type

ref (subject category)
art (subject category)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

Articles in the publication: Annals of Clinic ...

By the university: University of Gothenburg; Royal Institute of Technology; Karolinska Institutet; Uppsala University

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