have been downloaded. ADNI contributes data to a number of consortia and big data projects which have the potential to unlock many of the mysteries of neurological diseases. It shares imaging and genetic data with the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium which uses imaging genetics to study 12 major brain diseases including schizophrenia, bipolar disease and depression. The ADNI dataset was also used as the "test" dataset in the Dialogue on Reverse Engineering Assessment and Methods (DREAM) Alzheimer's disease Big Data Challenge #1 for the discovery of novel predictive AD biomarkers. One measure of the success of this open data sharing approach is the number of scientific publications arising from ADNI data: currently over 1000 and a wide variety of fields including areas outside of Alzheimer's disease. Development of standardized protocols ADNI has developed standardized protocols that allow results from multiple centers both within the study and worldwide to be directly compared. These include methods for the acquisition and quality control of both MRI and PET scans on scanners differing in the vendor, software platform, and field strength, and also for the analysis of CSF biomarkers. The standardized methods are now used by pharmaceutical companies, and in clinical trials of preventive and disease modifying AD treatments. Biomarker trajectories throughout disease progression An initial goal of ADNI was to understand the development of AD pathology by tracking imaging and CSF biomarkers throughout disease progression according to the amyloid hypothesis. A model of how different AD biomarkers change during the development of the AD proposed that biomarkers become abnormal in the following order: β-amyloid (indicating deposition of amyloid in plaques outside the cell, measured in CSF and by amyloid PET) Tau (indicating the formation of tau fibrils with the neurons) Glucose metabolism (measured on PET, indicating damage to neurons) Structural MRI (indicating damage to brain structure) Cognitive impairment This model has been largely validated using longitudinal ADNI data in patients who have abnormal levels of amyloid deposition, consistent with the amyloid hypothesis. Other significant findings Studies using ADNI cross-sectional and longitudinal MRI, PET, genetics, cognitive, biological fluid, and autopsy data have reported that: AD pathology is already present in people with no outward sign of memory loss. These cognitively normal people may already have subtle brain atrophy. AD progresses in a typical pattern, beginning in the entorhinal cortex in the preclinical AD, spreading to other regions affecting memory, then