The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

Ju-Hee Kang; Magdalena Korecka; Michal J Figurski; Jon B Toledo; Kaj Blennow; Henrik Zetterberg; Teresa Waligorska; Magdalena Brylska; Leona Fields; Nirali Shah; Holly Soares; Robert A Dean; Hugo Vanderstichele; Ronald C Petersen; Paul S Aisen; Andrew J Saykin; Michael W Weiner; John Q Trojanowski; Leslie M Shaw; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.jalz.2015.05.003

The Alzheimer's Disease Neuroimaging Initiative 2 Biomarker Core: A review of progress and plans

Alzheimers Dement. 2015 Jul;11(7):772-91. doi: 10.1016/j.jalz.2015.05.003.

Authors

Ju-Hee Kang¹, Magdalena Korecka², Michal J Figurski², Jon B Toledo³, Kaj Blennow⁴, Henrik Zetterberg⁵, Teresa Waligorska², Magdalena Brylska², Leona Fields², Nirali Shah², Holly Soares⁶, Robert A Dean⁷, Hugo Vanderstichele⁸, Ronald C Petersen⁹, Paul S Aisen¹⁰, Andrew J Saykin¹¹, Michael W Weiner¹², John Q Trojanowski¹³, Leslie M Shaw¹⁴; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ 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.
² Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
³ 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.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden.
⁵ 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.
⁶ Bristol Myers Squibb, Wallingford, CT, USA.
⁷ Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
⁸ Biomarkable bvba, Gent, Belgium.
⁹ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
¹⁰ Department of Neurosciences, University of California, San Diego, San Diego, CA, USA.
¹¹ 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.
¹² 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.
¹³ 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.
¹⁴ 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.

Abstract

Introduction: 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.

Discussion: Further studies will refine this model and enable the use of biomarkers studied in ADNI clinically and in disease-modifying therapeutic trials.

Keywords: ADNI; Alzheimer's disease; Aβ(1–42); Biomarkers; Cerebrospinal fluid; Disease-modifying therapy; Immunoassay; Mild cognitive impairment; Plasma; Tau.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Alzheimer Disease / cerebrospinal fluid*
Alzheimer Disease / diagnosis*
Amyloid beta-Peptides / cerebrospinal fluid*
Databases, Bibliographic / statistics & numerical data
Humans
Peptide Fragments / cerebrospinal fluid*
tau Proteins / cerebrospinal fluid*

Substances

Amyloid beta-Peptides
Peptide Fragments
amyloid beta-protein (1-42)
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding