title: The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans.
abstract: BACKGROUND
  We describe Alzheimer's Disease Neuroimaging Initiative (ADNI) Biomarker Core progress including: the Biobank; cerebrospinal fluid (CSF) amyloid beta (Aβ1-42), t-tau, and p-tau181 analytical performance, definition of Alzheimer's disease (AD) profile for plaque, and tangle burden detection and increased risk for progression to AD; AD disease heterogeneity; progress in standardization; and new studies using ADNI biofluids.
  
  
  METHODS
  Review publications authored or coauthored by ADNI Biomarker core faculty and selected non-ADNI studies to deepen the understanding and interpretation of CSF Aβ1-42, t-tau, and p-tau181 data.
  
  
  RESULTS
  CSF AD biomarker measurements with the qualified AlzBio3 immunoassay detects neuropathologic AD hallmarks in preclinical and prodromal disease stages, based on CSF studies in non-ADNI living subjects followed by the autopsy confirmation of AD. Collaboration across ADNI cores generated the temporal ordering model of AD biomarkers varying across individuals because of genetic/environmental factors that increase/decrease resilience to AD pathologies.
  
  
  CONCLUSIONS
  Further studies will refine this model and enable the use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic trials.
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pharmacology and Clinical Pharmacology, Hypoxia-Related Disease Research Center, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Korecka
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Figurski
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Toledo
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Waligorska
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Brylska
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Leona
authors.initials: L
authors.lastname: Fields
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Nirali
authors.initials: N
authors.lastname: Shah
authors.affiliation: Bristol Myers Squibb, Wallingford, CT, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Soares
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Dean
authors.affiliation: Biomarkable bvba, Gent, Belgium.
authors.forename: Hugo
authors.initials: H
authors.lastname: Vanderstichele
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.affiliation: Department of Neurosciences, University of California, San Diego, San Diego, CA, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Aisen
authors.affiliation: Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Saykin
authors.affiliation: Department of Radiology, Medicine and Psychiatry, University of California, San Francisco, CA, USA; Department of Veterans Affairs Medical Center, San Francisco, San Francisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA; Department of Neurology, Morris K. Udall Center of Excellence for Parkinson's Disease Research, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: Leslie.Shaw2@uphs.upenn.edu.
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Shaw
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D006801:Humans; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: ADNI; Alzheimer's disease; Aβ(1–42); Biomarkers; Cerebrospinal fluid; Disease-modifying therapy; Immunoassay; Mild cognitive impairment; Plasma; Tau