TY - JOUR
T1 - Elevated CSF GAP-43 is Alzheimer's disease specific and associated with tau and amyloid pathology
AU - Sandelius, Åsa
AU - Portelius, Erik
AU - Källén, Åsa
AU - Zetterberg, Henrik
AU - Rot, Uros
AU - Olsson, Bob
AU - Toledo, Jon B.
AU - Shaw, Leslie M.
AU - Lee, Virginia M.Y.
AU - Irwin, David J.
AU - Grossman, Murray
AU - Weintraub, Daniel
AU - Chen-Plotkin, Alice
AU - Wolk, David A.
AU - McCluskey, Leo
AU - Elman, Lauren
AU - Kostanjevecki, Vesna
AU - Vandijck, Manu
AU - McBride, Jennifer
AU - Trojanowski, John Q.
AU - Blennow, Kaj
N1 - Funding Information:
H.Z. is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Ventures-based platform company at the University of Gothenburg, and has served at advisory boards for Roche Diagnostics, Eli Lilly, and Pharmasum Therapeutics. K.B. has served as a consultant or at advisory boards for Alzheon, Biogen, Eli Lilly, Fujirebio Europe, IBL International, and Roche Diagnostics and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg. V.K. and M.V. are employees of Fujirebio Europe NV. D.A.W. has personal fees for consultation from GE Healthcare; grants from Avid Radiopharmaceuticals, Eli Lilly, Merck, Functional Neuromodulation, and Biogen outside the submitted work. The remaining authors have no conflicts to declare.
Funding Information:
The authors are grateful to Stiftelsen för gamla tjänarinnor, Demensfonden, Stiftelsen Sigurd och Elsa Goljes Minne, the Swedish and European Research Councils, Swedish State Support for Clinical Research (ALFGBG), Frimurarestiftelsen, Alzheimerfonden, Hjärnfonden, the Torsten Söderberg Foundation, and the Knut and Alice Wallenberg Foundation for funding. The funding sources had no involvement in the study.
Publisher Copyright:
© 2018 The Authors
PY - 2019/1
Y1 - 2019/1
N2 - Introduction: The level of the presynaptic protein growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) has previously been shown to be increased in Alzheimer's disease (AD) and thus may serve as an outcome measure in clinical trials and facilitate earlier disease detection. Methods: We developed an enzyme-linked immunosorbent assay for CSF GAP-43 and measured healthy controls (n = 43), patients with AD (n = 275), or patients with other neurodegenerative diseases (n = 344). In a subpopulation (n = 93), CSF GAP-43 concentrations from neuropathologically confirmed cases were related to Aβ plaques, tau, α-synuclein, and TDP-43 pathologies. Results: GAP-43 was significantly increased in AD compared to controls and most neurodegenerative diseases and correlated with the magnitude of neurofibrillary tangles and Aβ plaques in the hippocampus, amygdala, and cortex. GAP-43 was not associated to α-synuclein or TDP-43 pathology. Discussion: The presynaptic marker GAP-43 is associated with both diagnosis and neuropathology of AD and thus may be useful as a sensitive and specific biomarker for clinical research.
AB - Introduction: The level of the presynaptic protein growth-associated protein 43 (GAP-43) in cerebrospinal fluid (CSF) has previously been shown to be increased in Alzheimer's disease (AD) and thus may serve as an outcome measure in clinical trials and facilitate earlier disease detection. Methods: We developed an enzyme-linked immunosorbent assay for CSF GAP-43 and measured healthy controls (n = 43), patients with AD (n = 275), or patients with other neurodegenerative diseases (n = 344). In a subpopulation (n = 93), CSF GAP-43 concentrations from neuropathologically confirmed cases were related to Aβ plaques, tau, α-synuclein, and TDP-43 pathologies. Results: GAP-43 was significantly increased in AD compared to controls and most neurodegenerative diseases and correlated with the magnitude of neurofibrillary tangles and Aβ plaques in the hippocampus, amygdala, and cortex. GAP-43 was not associated to α-synuclein or TDP-43 pathology. Discussion: The presynaptic marker GAP-43 is associated with both diagnosis and neuropathology of AD and thus may be useful as a sensitive and specific biomarker for clinical research.
KW - Alzheimer's disease
KW - CSF biomarker
KW - Differential diagnosis
KW - Enzyme-linked immunosorbent assay
KW - GAP-43
UR - http://www.scopus.com/inward/record.url?scp=85056288692&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056288692&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2018.08.006
DO - 10.1016/j.jalz.2018.08.006
M3 - Article
C2 - 30321501
AN - SCOPUS:85056288692
SN - 1552-5260
VL - 15
SP - 55
EP - 64
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 1
ER -