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Elevated CSF GAP‐43 is Alzheimer's disease specific and associated with tau and amyloid pathology
Author(s) -
Sandelius Åsa,
Portelius Erik,
Källén Åsa,
Zetterberg Henrik,
Rot Uros,
Olsson Bob,
Toledo Jon B.,
Shaw Leslie M.,
Lee Virginia M. Y.,
Irwin David J.,
Grossman Murray,
Weintraub Daniel,
ChenPlotkin Alice,
Wolk David A.,
McCluskey Leo,
Elman Lauren,
Kostanjevecki Vesna,
Vandijck Manu,
McBride Jennifer,
Trojanowski John Q.,
Blennow Kaj
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.08.006
Subject(s) - neuropathology , cerebrospinal fluid , pathology , biomarker , alzheimer's disease , medicine , tau protein , gap 43 protein , disease , neurofibrillary tangle , hippocampus , senile plaques , immunohistochemistry , biology , biochemistry
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.