Review

. 2017 May;13(5):561-571.

doi: 10.1016/j.jalz.2016.10.006. Epub 2016 Dec 5.

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

Michael W Weiner¹, Dallas P Veitch², Paul S Aisen³, Laurel A Beckett⁴, Nigel J Cairns⁵, Robert C Green⁶, Danielle Harvey⁴, Clifford R Jack Jr⁷, William Jagust⁸, John C Morris³, Ronald C Petersen⁹, Jennifer Salazar³, Andrew J Saykin¹⁰, Leslie M Shaw¹¹, Arthur W Toga¹², John Q Trojanowski¹³; Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA; Department of Radiology, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: michael.weiner@ucsf.edu.
² Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
³ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
⁴ Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA, USA.
⁵ Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA; Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
⁶ Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
⁸ Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA.
⁹ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
¹⁰ Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
¹¹ Tailored Therapeutics, Eli Lilly and Company, Indianapolis, IN, USA.
¹² Laboratory of Neuroimaging, Institute of Neuroimaging and Informatics, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
¹³ Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Alzheimer's Disease Core Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Udall Parkinson's Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

PMID: 27931796
PMCID: PMC5536850
DOI: 10.1016/j.jalz.2016.10.006

Review

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

Michael W Weiner et al. Alzheimers Dement. 2017 May.

. 2017 May;13(5):561-571.

doi: 10.1016/j.jalz.2016.10.006. Epub 2016 Dec 5.

Authors

Affiliations

¹ Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA; Department of Radiology, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; Department of Psychiatry, University of California, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, CA, USA. Electronic address: michael.weiner@ucsf.edu.
² Department of Veterans Affairs Medical Center, Center for Imaging of Neurodegenerative Diseases, San Francisco, CA, USA.
³ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
⁴ Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, CA, USA.
⁵ Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA; Department of Neurology, Washington University School of Medicine, Saint Louis, MO, USA.
⁶ Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Department of Radiology, Mayo Clinic, Rochester, MN, USA.
⁸ Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA.
⁹ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
¹⁰ Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
¹¹ Tailored Therapeutics, Eli Lilly and Company, Indianapolis, IN, USA.
¹² Laboratory of Neuroimaging, Institute of Neuroimaging and Informatics, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
¹³ Institute on Aging, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Alzheimer's Disease Core Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Udall Parkinson's Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

PMID: 27931796
PMCID: PMC5536850
DOI: 10.1016/j.jalz.2016.10.006

Abstract

Introduction: The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI-3, which began on August 1, 2016, is a 5-year renewal of the current ADNI-2 study.

Methods: ADNI-3 will follow current and additional subjects with normal cognition, mild cognitive impairment, and AD using innovative technologies such as tau imaging, magnetic resonance imaging sequences for connectivity analyses, and a highly automated immunoassay platform and mass spectroscopy approach for cerebrospinal fluid biomarker analysis. A Systems Biology/pathway approach will be used to identify genetic factors for subject selection/enrichment. Amyloid positron emission tomography scanning will be standardized using the Centiloid method. The Brain Health Registry will help recruit subjects and monitor subject cognition.

Results: Multimodal analyses will provide insight into AD pathophysiology and disease progression.

Discussion: ADNI-3 will aim to inform AD treatment trials and facilitate development of AD disease-modifying treatments.

Keywords: Alzheimer's disease; Amyloid phenotyping; Brain Health Registry; Centiloid method; Clinical trial biomarkers; Functional connectivity; Tau imaging.

PubMed Disclaimer

Conflict of interest statement

Conflicts of interest:

Dallas P. Veitch has no conflicts of interest to report.

Dr. Jack has provided consulting services for Eli Lily and owns stock in Johnson and Johnson.

Dr. Jagust consults for Genentech Inc., Banner Alzheimer Institute, Bioclinica, and Novartis

Dr. Petersen consults for Roche Inc., Merck Inc., Genetech Inc., and Biogen Inc.

Figures

**Figure 1. In-vivo Braak staging**
Braak staging of healthy young adults (YA, n=5), healthy older adults (OA, n=15) and AD patients (n=15) based on AV-1451 Braak region of interest uptake, with participant characterization by in-vivo assigned Braak stage. ICV, intracranial volume. Values for Mini Mental State Exam (MMSE), Pittsburgh compound B distribution volume ratio (PIB DVR) index, and hippocampal volume are mean (SD). Reproduced with permission from [65].

**Figure 2. Comparison of Aβ_1–42 results (pg/mL) for 10 patient CSF samples**
UGOT, University of Gothenburg; UPENN, University of Pennsylvania. Each laboratory used their multiple reaction monitoring/tandem mass spectrometry method [72, 85], each approved by the Joint Committee for Traceability in Laboratory Medicine as reference methods.

See this image and copyright information in PMC

References

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1. Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, Cedarbaum J, et al. 2014 Update of the Alzheimer’s Disease Neuroimaging Initiative: A review of papers published since its inception. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2015;11:e1–e120. - PMC - PubMed
1. Mueller SG, Weiner MW, Thal LJ, Petersen RC, Jack C, Jagust W, et al. The Alzheimer’s disease neuroimaging initiative. Neuroimaging Clin N Am. 2005;15:869–77. xi–xii. - PMC - PubMed
1. Weiner MW, Aisen PS, Jack CR, Jr, Jagust WJ, Trojanowski JQ, Shaw L, et al. The Alzheimer’s disease neuroimaging initiative: progress report and future plans. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2010;6:202–11 e7. - PMC - PubMed

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The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

Affiliations

The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical