Journal article

Sequence of Alzheimer disease biomarker changes in cognitively normal adults A cross-sectional study

Jingqin Luo, Folasade Agboola, Elizabeth Grant, Colin L Masters, Marilyn S Albert, Sterling C Johnson, Eric M McDade, Jonathan Voglein, Anne M Fagan, Tammie Benzinger, Parinaz Massoumzadeh, Jason Hassenstab, Randall J Bateman, John C Morris, Richard J Perrin, Jasmeer Chhatwal, Mathias Jucker, Bernardino Ghetti, Carlos Cruchaga, Neill R Graff-Radford Show all



OBJECTIVE: To determine the ordering of changes in Alzheimer disease (AD) biomarkers among cognitively normal individuals. METHODS: Cross-sectional data, including CSF analytes, molecular imaging of cerebral fibrillar β-amyloid (Aβ) with PET using the [11C] benzothiazole tracer Pittsburgh compound B (PiB), MRI-based brain structures, and clinical/cognitive outcomes harmonized from 8 studies, collectively involving 3,284 cognitively normal individuals 18 to 101 years of age, were analyzed. The age at which each marker exhibited an accelerated change (called the change point) was estimated and compared across the markers. RESULTS: Accelerated changes in CSF Aβ1-42 (Aβ42) occurred at 48.28 year..

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Awarded by National Institute on Aging (NIA)

Awarded by NIA

Awarded by Neuroimaging Informatics and Analysis Center

Awarded by DIAN - NIA

Funding Acknowledgements

This study was supported by National Institute on Aging (NIA) grant R01 AG053550 (Dr. Xiong) and NIA grants P50 AG005681, P01AG026276, and P01 AG0399131 (Dr. Morris), UF1AG032438 (Dr. Bateman), U19-AGO33655 and R01 AG059869 (Dr. Albert), R01 AG027161 and R01 AG021155 (Dr. Johnson), and Australian Commonwealth Scientific Industrial Research Organization (Dr. Masters).The AIBL study ( was supported by the Alzheimer's Association (United States), the Alzheimer's Drug Discovery Foundation, an anonymous foundation, the Science and Industry Endowment Fund, the Dementia Collaborative Research Centres, the Victorian Government's Operational Infrastructure Support program, the McCusker Alzheimer's Research Foundation, the National Health and Medical Research Council, and the Yulgilbar Foundation, plus numerous commercial interactions that supported data collection and analysis. Image processing was supported in part by the Neuroimaging Informatics and Analysis Center (1P30NS098577) and R01 EB009352. Data collection and sharing for this project were supported by DIAN (UF1AG032438) funded by the NIA, the German Center for Neurodegenerative Diseases, and Raul Carrea Institute for Neurological Research. Partial support was provided by the Research and Development Grants for Dementia from Japan Agency forMedical Research and Development, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute. This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications.