CSF profiling of the human brain enriched proteome reveals associations of neuromodulin and neurogranin to Alzheimer's disease.
This study is part of a larger effort aiming to expand the knowledge of brain-enriched proteins in human cerebrospinal fluid (CSF) and to provide novel insight into the relation between such proteins and different neurodegenerative diseases.



Here 280 brain-enriched proteins in CSF from patients with Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are profiled. In total, 441 human samples of ventricular CSF collected post mortem and lumbar CSF collected ante mortem are analyzed using 376 antibodies in a suspension bead array setup, utilizing a direct labelling approach.



Among several proteins displaying differentiated profiles between sample groups, we focus here on two synaptic proteins, neuromodulin (GAP43) and neurogranin (NRGN). They are both found at elevated levels in CSF from AD patients in two independent cohorts, providing disease-associated profiles in addition to verifying and strengthening previously observed patterns. Increased levels are also observed for patients for whom the AD diagnosis was not established at the time of sampling.



These findings indicate that analyzing the brain-enriched proteins in CSF is of particular interest to increase the understanding of the CSF proteome and its relation to neurodegenerative disorders. In addition, this study lends support to the notion that measurements of these synaptic proteins could potentially be of great relevance in future diagnostic tests for AD.
Affinity Proteomics, SciLifeLab, KTH-Royal Institute of Technology, Stockholm, Sweden.
Julia
J
Remnestål
Affinity Proteomics, SciLifeLab, KTH-Royal Institute of Technology, Stockholm, Sweden.
David
D
Just
SciLifeLab, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Nicholas
N
Mitsios
Affinity Proteomics, SciLifeLab, KTH-Royal Institute of Technology, Stockholm, Sweden.
Claudia
C
Fredolini
SciLifeLab, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Jan
J
Mulder
Affinity Proteomics, SciLifeLab, KTH-Royal Institute of Technology, Stockholm, Sweden.
Jochen M
JM
Schwenk
Affinity Proteomics, SciLifeLab, KTH-Royal Institute of Technology, Stockholm, Sweden.
Mathias
M
Uhlén
Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, Uppsala, Sweden.
Kim
K
Kultima
Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
Martin
M
Ingelsson
Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
Lena
L
Kilander
Department of Public Health/Geriatrics, Uppsala University, Uppsala, Sweden.
Lars
L
Lannfelt
Translational Neuropharmacology, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Per
P
Svenningsson
Department of Anaesthesiology and Intensive Care, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
Bengt
B
Nellgård
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
Henrik
H
Zetterberg
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.|Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
Kaj
K
Blennow
Affinity Proteomics, SciLifeLab, KTH-Royal Institute of Technology, Stockholm, Sweden.
Peter
P
Nilsson
Affinity Proteomics, SciLifeLab, KTH-Royal Institute of Technology, Stockholm, Sweden.
Anna
A
Häggmark-Månberg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D019922:GAP-43 Protein / Q000134:cerebrospinal fluid*; D006801:Humans; D020961:Lewy Body Disease / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D051579:Neurogranin / Q000134:cerebrospinal fluid*; D010300:Parkinson Disease / Q000134:cerebrospinal fluid; D040901:Proteomics
D019922:GAP-43 Protein; D051579:Neurogranin
Alzheimer's disease; Cerebrospinal fluid; Neurogranin; Neuromodulin; Neuroproteomics