University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Florey Department of Neuroscience and Mental Health
  • Florey Department of Neuroscience and Mental Health - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Florey Department of Neuroscience and Mental Health
  • Florey Department of Neuroscience and Mental Health - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

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

    Thumbnail
    Download
    Published version (9.699Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    14
    13
    Author
    Lee, S; Zimmerman, ME; Narkhede, A; Nasrabady, SE; Tosto, G; Meier, IB; Benzinger, TLS; Marcus, DS; Fagan, AM; Fox, NC; ...
    Date
    2018-05-09
    Source Title
    PLoS One
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Masters, Colin
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Lee, S., Zimmerman, M. E., Narkhede, A., Nasrabady, S. E., Tosto, G., Meier, I. B., Benzinger, T. L. S., Marcus, D. S., Fagan, A. M., Fox, N. C., Cairns, N. J., Holtzman, D. M., Buckles, V., Ghetti, B., McDade, E., Martins, R. N., Saykin, A. J., Masters, C. L., Ringman, J. M. ,... Brickman, A. M. (2018). White matter hyperintensities and the mediating role of cerebral amyloid angiopathy in dominantly-inherited Alzheimer's disease. PLOS ONE, 13 (5), https://doi.org/10.1371/journal.pone.0195838.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255051
    DOI
    10.1371/journal.pone.0195838
    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 age = 41.1 years) included 112 with an AD mutation and 63 first-degree non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) and analyzed baseline MRI data for WMH volume and presence of cerebral microbleeds. Mixed effects regression and tests of mediation were used to examine microbleed and WMH differences between carriers and non-carriers and to test the whether the association between WMH and mutation status is dependent on the presence of microbleeds. RESULTS: Mutation carriers were more likely to have microbleeds than non-carriers (p<0.05) and individuals with microbleeds had higher WMH volume than those without (p<0.05). Total WMH volume was increased in mutation carriers compared with non-carriers, up to 20 years prior to EYO, after controlling for microbleed status, as we demonstrated previously. Formal testing of mediation demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds (p = 0.03) but a significant direct effect of WMH remained (p = 0.02) after controlling for presence of microbleeds. DISCUSSION: Although there is some co-dependency between WMH and microbleeds, the observed increases in WMH among mutation carriers does not appear to be fully mediated by this marker of CAA. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45689]
    • Florey Department of Neuroscience and Mental Health - Research Publications [1052]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors