White matter integrity is associated with cerebrospinal fluid markers of Alzheimer's disease in normal adults

Brian T. Gold, Zude Zhu, Christopher A. Brown, Anders H. Andersen, Mary Jo LaDu, Leon Tai, Greg A. Jicha, Richard J. Kryscio, Steven Estus, Peter T. Nelson, Steve W. Scheff, Erin Abner, Frederick A. Schmitt, Linda J. Van Eldik, Charles D. Smith

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


We explored whether white matter (WM) integrity in cognitively normal (CN) older adults is associated with cerebrospinal fluid (CSF) markers of Alzheimer's disease pathology. Twenty CN older adults underwent lumbar puncture and magnetic resonance imaging within a few days of each other. Analysis of diffusion tensor imaging data involved a priori region of interest and voxelwise approaches. The region of interest results revealed a positive correlation between CSF measures of amyloid-beta (Aβ42 and Aβ42/p-Tau181) and WM integrity in the fornix, a relationship which persisted after controlling for hippocampal volume and fornix volume. Lower WM integrity in the same portion of the fornix was also associated with reduced performance on the Digit Symbol test. Subsequent exploratory voxelwise analyses indicated a positive correlation between CSF Aβ42/p-Tau181 and WM integrity in bilateral portions of the fornix, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and in the corpus callosum and left inferior longitudinal fasciculus. Our results link lower WM microstructural integrity in CN older adults with CSF biomarkers of Alzheimer's disease and suggest that this association in the fornix may be independent of volumetric measures.

Original languageEnglish
Pages (from-to)2263-2271
Number of pages9
JournalNeurobiology of Aging
Issue number10
StatePublished - Oct 2014

Bibliographical note

Funding Information:
This study was supported by the National Institute on Aging of the National Institutes of Health under award numbers ( P30 AG028383 , P01 AG030128 , R01 AG033036 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of these granting agencies. The authors thank Beverly Meacham for her assistance in scanning participants. Most of all, they wish to thank the dedicated volunteers at the Sanders-Brown Center on Aging for their participation in this research.


  • CSF
  • DTI
  • Normal older adults
  • Preclinical AD
  • White matter

ASJC Scopus subject areas

  • General Neuroscience
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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