@article{df123a9937344482abfde036bb5d4da2,
title = "Blood-based protein predictors of dementia severity as measured by δ: Replication across biofluids and cohorts",
abstract = "Introduction: Dementia severity can be empirically described by the latent dementia phenotype “δ” and its various composite “homologs”. We have explored δ's blood-based protein biomarkers in the Texas Alzheimer's Research and Care Consortium (TARCC) study. However, it would be convenient to replicate those associations in the Alzheimer's Disease Neuroimaging Initiative (ADNI). To this end, we recently engineered a δ homolog from observed cognitive performance measures common to both projects (i.e., “dT2A”). Methods: We used nine rationally chosen peripheral blood-based protein biomarkers as indicators of a latent variable “INFLAMMATION”. We then associated that construct with dT2A in structural equation models adjusted for age, gender, depressive symptoms, and apolipoprotein E (APOE) ε4 allelic burden. Significant factor loadings and INFLAMMATION's association with dT2A were confirmed in random splits of TARCC's relatively large sample, and across biofluids in the ADNI. Results: Nine proteins measured in serum (TARCC) or plasma (ADNI) explained ≅10% of dT2A's variance in both samples, independently of age, APOE, education, and gender. All loaded significantly on INFLAMMATION, and positively or negatively, depending on their known roles are PRO- or ANTI-inflammatory proteins, respectively. The parameters of interest were confirmed across random 50% splits of the TARCC's sample, and replicated across biofluids in the ADNI. Discussion: These results suggest that SEM can be used to replicate biomarker findings across samples and biofluids, and that a substantial fraction of dementia's variance is attributable to peripheral blood-based protein levels.",
keywords = "ADNI, Aging, Cognition, Dementia, Intelligence, TARCC, g",
author = "Royall, {Donald R.} and Bishnoi, {Ram J.} and Palmer, {Raymond F.} and Valory Pavlik and Paul Massman and Eveleen Darby and Monica Rodriguear and Ansari, {Aisha Khaleeq} and DeToledo, {John C.} and Hemachandra Reddy and Henrick Wilms and Kim Johnson and Victoria Perez and Thomas Fairchild and Janice Knebl and O'Bryant, {Sid E.} and Hall, {James R.} and Leigh Johnson and Barber, {Robert C.} and Douglas Mains and Lisa Alvarez and Munro Cullum and Roger Rosenberg and Benjamin Williams and Mary Quiceno and Joan Reisch and Hynan, {Linda S.} and Ryan Huebinger and Janet Smith and Trung Nguyen and Donald Royall and Raymond Palmer and Marsha Polk and Alan Stevens and Marcia Ory and David Paydarfar and John Bertelson and Martin Woon and Gayle Ayres and Alyssa Aguirre and Wilhelmsen, {Kirk C.} and Tilson, {Jeffrey L.}",
note = "Funding Information: Data collection and sharing for 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 ). The 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 the ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health. Funding Information: This project was supported in part by funding provided to the Texas Alzheimer's Research and Care Consortium by the Darrell K Royal Texas Alzheimer's Initiative, directed by the Texas Council on Alzheimer's Disease and Related Disorders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: Authors' contributions: D.R.R. designed the study, interpreted the analysis, and drafted and revised the manuscript. R.B. prepared data sets and revised the manuscript for intellectual content. R.F.P. performed the analysis and revised the manuscript for intellectual content. This project was supported in part by funding provided to the Texas Alzheimer's Research and Care Consortium by the Darrell K Royal Texas Alzheimer's Initiative, directed by the Texas Council on Alzheimer's Disease and Related Disorders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Investigators from the Texas Alzheimer's Research and Care Consortium: Baylor College of Medicine: Valory Pavlik PhD, Paul Massman PhD, Eveleen Darby MA/MS, Monica Rodriguear MA, Aisha Khaleeq Ansari MD; Texas Tech University Health Sciences Center: John C. DeToledo MD, Hemachandra Reddy PhD, Henrick Wilms MD, PhD, Kim Johnson PhD, Victoria Perez; University of North Texas Health Science Center: Thomas Fairchild PhD, Janice Knebl DO, Sid E. O'Bryant PhD, James R. Hall PhD, Leigh Johnson PhD, Robert C. Barber PhD, Douglas Mains DrPH, Lisa Alvarez; University of Texas Southwestern Medical Center: Munro Cullum PhD, Roger Rosenberg MD, Benjamin Williams MD, PhD, Mary Quiceno MD, Joan Reisch PhD, Linda S. Hynan PhD, Ryan Huebinger PhD, Janet Smith, Trung Nguyen MD, PhD; University of Texas Health Science Center?San Antonio: Donald Royall MD, Raymond Palmer PhD, Marsha Polk; Texas A&M University Health Science Center: Alan Stevens PhD, Marcia Ory PhD/MPH; University of Texas at Austin/Dell Medical School: David Paydarfar MD, John Bertelson MD, Martin Woon PhD, Gayle Ayres DO; Alyssa Aguirre LCSW; University of North Carolina: Kirk C. Wilhelmsen MD, PhD, Jeffrey L. Tilson PhD. Data collection and sharing for 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). The 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 the 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. The ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Dr. Royall has disclosed his co-invention of ?, its homologs and orthologs to the University of Texas Health Science Center at San Antonio (UTHSCSA), which has filed patent application 2012.039.US1.HSCS and provisional patents 61/603,226 and 61/671,858 relating to the latent variable d's construction and biomarkers. Dr. Palmer has disclosed his co-invention of ?, its homologs and orthologs to the UTHSCSA. These data were previously presented at the 2018 International Congress on Alzheimer's Disease (ICAD). Chicago, IL, 2018. Royall DR, Bishnoi R, Palmer RF. [abstract] Blood-based protein predictors of dementia severity as measured by ?: Replication across biofluids and cohorts. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 2018;14;P649-650. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = dec,
doi = "10.1016/j.dadm.2019.09.002",
language = "English (US)",
volume = "11",
pages = "763--774",
journal = "Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring",
issn = "2352-8729",
publisher = "Elsevier BV",
}
