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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

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Free PMC article
Review

The Alzheimer's Disease Neuroimaging Initiative 3: Continued Innovation for Clinical Trial Improvement

Michael W Weiner et al. Alzheimers Dement. .
Free PMC article

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.

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
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
Figure 2. Comparison of Aβ1–42 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.

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