TY - JOUR
T1 - Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer's disease
AU - ADNI
AU - Sutphen, Courtney L.
AU - McCue, Lena
AU - Herries, Elizabeth M.
AU - Xiong, Chengjie
AU - Ladenson, Jack H.
AU - Holtzman, David M.
AU - Fagan, Anne M.
N1 - Funding Information:
Funding for this study was obtained through NIH grants P50AG005681 (D.M.H. and A.M.F.), P01AG003991 (D.M.H. and A.M.F.), P01AG026276 (D.M.H. and A.M.F.), and a grant from Eli Lilly (D.M.H.). Data collection and sharing for this project were 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:
Funding for this study was obtained through NIH grants P50AG005681 (D.M.H. and A.M.F.), P01AG003991 (D.M.H. and A.M.F.), P01AG026276 (D.M.H. and A.M.F.), and a grant from Eli Lilly (D.M.H.). Data collection and sharing for this project were 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:
Conflicts of interest: C.L.S., L.M., and E.M.H. report no conflicts. C.H. is supported by NIH grants including P50AG005681, P01AG003991, P01AG026276, R01AG034119, and R01AG053550. He reports no conflicts. J.H.L. is named on patents related to biomarkers for Alzheimer's disease. These patents and any resulting licenses are being administered by Washington University in accordance with University policies. D.M.H. is supported by NIH grants including P50AG005681, P01AG003991, and P01AG026276. He is on the scientific advisory board of C2N Diagnostics. He is a consultant over the last year for Genentech, AbbVie, Neurophage, Denali, and Eli Lilly. He reports no conflicts. A.M.F. is supported by the NIH grants, including P50AG005681, P01AG003991, P01AG026276, and UF01AG03243807. She is on the Scientific Advisory Boards for Roche Diagnostics, IBL International, and AbbVie and consults for Biogen, DiamiR, LabCorp, and Araclon Biotech/Grifols. She reports no conflicts.
Publisher Copyright:
© 2018 The Authors
PY - 2018/7
Y1 - 2018/7
N2 - Introduction: Individuals in early stages of Alzheimer's disease are a targeted population for secondary prevention trials aimed at preserving normal cognition. Understanding within-person biomarker(s) change over time is critical for trial enrollment and design. Methods: Longitudinal cerebrospinal fluid samples from the Alzheimer's Disease Neuroimaging Initiative were assayed for novel markers of neuronal/synaptic injury (visinin-like protein 1, Ng, and SNAP-25) and neuroinflammation (YKL-40) and compared with β amyloid 42, tau, and phospho-tau181. General linear mixed models were used to compare within-person rates of change in three clinical groups (cognitively normal, mild cognitive impairment, and Alzheimer's disease) further defined by β amyloid status. Results: Levels of injury markers were highly positively correlated. Despite elevated baseline levels as a function of clinical status and amyloid-positivity, within-person decreases in these measures were observed in the early symptomatic, amyloid-positive Alzheimer's disease group. Discussion: Knowledge of within-person biomarker change will impact interpretation of biomarker outcomes in clinical trials that are dependent on disease stage.
AB - Introduction: Individuals in early stages of Alzheimer's disease are a targeted population for secondary prevention trials aimed at preserving normal cognition. Understanding within-person biomarker(s) change over time is critical for trial enrollment and design. Methods: Longitudinal cerebrospinal fluid samples from the Alzheimer's Disease Neuroimaging Initiative were assayed for novel markers of neuronal/synaptic injury (visinin-like protein 1, Ng, and SNAP-25) and neuroinflammation (YKL-40) and compared with β amyloid 42, tau, and phospho-tau181. General linear mixed models were used to compare within-person rates of change in three clinical groups (cognitively normal, mild cognitive impairment, and Alzheimer's disease) further defined by β amyloid status. Results: Levels of injury markers were highly positively correlated. Despite elevated baseline levels as a function of clinical status and amyloid-positivity, within-person decreases in these measures were observed in the early symptomatic, amyloid-positive Alzheimer's disease group. Discussion: Knowledge of within-person biomarker change will impact interpretation of biomarker outcomes in clinical trials that are dependent on disease stage.
KW - Cerebrospinal fluid
KW - Longitudinal biomarkers
KW - Neuronal injury
UR - http://www.scopus.com/inward/record.url?scp=85044568072&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2018.01.012
DO - 10.1016/j.jalz.2018.01.012
M3 - Article
C2 - 29580670
AN - SCOPUS:85044568072
SN - 1552-5260
VL - 14
SP - 869
EP - 879
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 7
ER -