TY - JOUR
T1 - Synaptic biomarkers in CSF aid in diagnosis, correlate with cognition and predict progression in MCI and Alzheimer's disease
AU - Alzheimer’s Disease Neuroimaging Initiative (ADNI)
AU - Galasko, Douglas
AU - Xiao, Meifang
AU - Xu, Desheng
AU - Smirnov, Denis
AU - Salmon, David P.
AU - Dewit, Nele
AU - Vanbrabant, Jeroen
AU - Jacobs, Dirk
AU - Vanderstichele, Hugo
AU - Vanmechelen, Eugeen
AU - Worley, Paul
N1 - Funding Information:
This work was supported by the National Institutes of Health [grant numbers AGO5131 , AG062429 , R35 NS097966-04 and R43AG064998 ] and the Alzheimer's Drug Discovery Foundation (ADDF). JB and EVM were supported by the Agency for Innovation by Science and Technology ( VLAIO , www.vlaio.be , grant number 140105 ). Data collection and sharing for the replication studies in this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) ( National Institutes of Health Grant U01 AG024904 ) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012 ). ADNI is funded by the National Institute on Aging , the National Institute of Biomedical Imaging and Bioengineering , and through generous contributions from the following: AbbVie , Alzheimer's Association ; Alzheimer's Drug Discovery Foundation ; Araclon Biotech ; BioClinica, Inc. ; Biogen ; Bristol-Myers Squibb Company ; CereSpir, Inc. ; Cogstate ; Eisai Inc. ; Elan Pharmaceuticals, Inc. ; Eli Lilly and Company ; EuroImmun ; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc. ; Fujirebio ; GE Healthcare ; IXICO Ltd. ; Janssen Alzheimer Immunotherapy Research & Development, LLC. ; Johnson & Johnson Pharmaceutical Research & Development LLC. ; Lumosity ; Lundbeck ; Merck & Co., Inc. ; Meso Scale Diagnostics, LLC. ; NeuroRx Research ; Neurotrack Technologies ; Novartis Pharmaceuticals Corporation ; Pfizer Inc. ; Piramal Imaging ; Servier ; Takeda Pharmaceutical Company ; and Transition Therapeutics . The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Funding Information:
This work was supported by the National Institutes of Health [grant numbers AGO5131, AG062429, R35 NS097966-04 and R43AG064998] and the Alzheimer's Drug Discovery Foundation (ADDF). JB and EVM were supported by the Agency for Innovation by Science and Technology (VLAIO, www.vlaio.be, grant number 140105). Data collection and sharing for the replication studies in this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co. Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Role of the funding source: Clinical and CSF data collected at UCSD is supported by NIH funding. Drs Vanmechelen, Vanderstichele, Vanbrabant and Mr DeWit and Jacobs are employees of ADx NeuroSciences, Ghent, Belgium. Hugo Vanderstichele is working in ADx NeuroSciences on behalf of Biomarkable. ADx provided assay kits for this study and performed the measurements of Aβ1-42, Tau, and SNAP25. ADx did not provide other material or funding. ADx co-authors contributed to study design, data analysis, and interpretation and to the writing of this report. MX, DX, PW co-founded CogNext, which develops biomarkers of memory consolidation. ADNI funding is described in the Acknowledgments.
Publisher Copyright:
© 2019 The Authors
PY - 2019
Y1 - 2019
N2 - Introduction: Amyloid, Tau, and neurodegeneration biomarkers can stage Alzheimer's Disease (AD). Synaptic biomarkers may help track cognition. Methods: In cognitively normal controls, Mild Cognitive Impairment (MCI) and AD, we investigated CSF biomarkers in relation to cognitive measures and as predictors of cognitive and global decline. Results: There were 90 normal controls (mean age 73.0, 58% women), 57 MCI (mean age 74.3, 35% women), and 46 AD (mean age 70.7, 41% women). CSF Aβ1-42 and Neuronal Pentraxin 2 (NPTX2) were decreased, and CSF Tau, neurogranin, and SNAP25 increased in AD versus controls. Aβ1-42/Tau or NPTX2/Tau discriminated AD and controls best. NPTX2/Tau correlated strongly with cognition in AD and MCI and predicted a 2–3-year decline. We replicated findings in the ADNI cohort. Discussion: CSF synaptic biomarkers, particularly NPTX2, which regulates synaptic homeostasis, relate to cognition and predict progression in AD beyond Aβ1-42 and Tau. This is relevant for prognosis and clinical trials.
AB - Introduction: Amyloid, Tau, and neurodegeneration biomarkers can stage Alzheimer's Disease (AD). Synaptic biomarkers may help track cognition. Methods: In cognitively normal controls, Mild Cognitive Impairment (MCI) and AD, we investigated CSF biomarkers in relation to cognitive measures and as predictors of cognitive and global decline. Results: There were 90 normal controls (mean age 73.0, 58% women), 57 MCI (mean age 74.3, 35% women), and 46 AD (mean age 70.7, 41% women). CSF Aβ1-42 and Neuronal Pentraxin 2 (NPTX2) were decreased, and CSF Tau, neurogranin, and SNAP25 increased in AD versus controls. Aβ1-42/Tau or NPTX2/Tau discriminated AD and controls best. NPTX2/Tau correlated strongly with cognition in AD and MCI and predicted a 2–3-year decline. We replicated findings in the ADNI cohort. Discussion: CSF synaptic biomarkers, particularly NPTX2, which regulates synaptic homeostasis, relate to cognition and predict progression in AD beyond Aβ1-42 and Tau. This is relevant for prognosis and clinical trials.
KW - Alzheimer's disease
KW - Biomarker
KW - Cerebrospinal fluid
KW - Prognosis
KW - Synapse
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U2 - 10.1016/j.trci.2019.11.002
DO - 10.1016/j.trci.2019.11.002
M3 - Article
C2 - 31853477
AN - SCOPUS:85076039825
SN - 2352-8737
VL - 5
SP - 871
EP - 882
JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions
JF - Alzheimer's and Dementia: Translational Research and Clinical Interventions
ER -