Journal article

White matter hyperintensities and the mediating role of cerebral amyloid angiopathy in dominantly-inherited Alzheimer's disease

Seonjoo Lee, Molly E Zimmerman, Atul Narkhede, Sara E Nasrabady, Giuseppe Tosto, Irene B Meier, Tammie LS Benzinger, Daniel S Marcus, Anne M Fagan, Nick C Fox, Nigel J Cairns, David M Holtzman, Virginia Buckles, Bernardino Ghetti, Eric McDade, Ralph N Martins, Andrew J Saykin, Colin L Masters, John M Ringman, Stefan Foerster Show all

PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2018

Abstract

INTRODUCTION: White matter hyperintensity (WMH) volume on MRI is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer's disease (AD). One potential explanation is that WMH, conventionally considered a marker of cerebrovascular disease, are a reflection of cerebral amyloid angiopathy (CAA) and that increased WMH in this population is a manifestation of this vascular form of primary AD pathology. We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between WMH and estimated symptom onset in individuals with and without autosomal dominant mutations for AD. PARTICIPANTS AND METHODS: Participants (n = 175, mean ..

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Grants

Awarded by NIH/NIA


Awarded by Dominantly Inherited Alzheimer's Network (DIAN) - National Institute on Aging (NIA)


Awarded by NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES


Awarded by NATIONAL CENTER FOR RESEARCH RESOURCES


Awarded by NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Awarded by NATIONAL INSTITUTE ON AGING


Funding Acknowledgements

This work was supported by NIH/NIA U19 AG032438. SL is supported by NIH/NIA AG051348. This work was supported by the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI), with partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S.L. is supported by NIH/NIA AG051348. Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer's Network (DIAN, UF1AG032438) funded by the National Institute on Aging (NIA), the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI), Partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI). This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. We acknowledge the altruism of the participants and their families and contributions of the DIAN research and support staff at each of the participating sites for their contributions to this study.