Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions

Neurobiol Aging. 2019 Dec;84:225-234. doi: 10.1016/j.neurobiolaging.2019.08.001. Epub 2019 Aug 9.


White matter hyperintensities (WMHs) are a common manifestation of cerebral small vessel disease. WMHs are also frequently observed in patients with familial and sporadic Alzheimer's disease, often with a particular posterior predominance. Whether amyloid and tau pathologies are linked to WMH occurrence is still debated. We examined whether cerebral amyloid and tau burden, reflected in cerebrospinal fluid amyloid-beta 1-42 (Aβ-42) and phosphorylated tau (p-tau), are related to WMH location in a cohort of 517 memory clinic patients. Two lesion mapping techniques were performed: voxel-based analyses and region of interest-based linear regression. Voxelwise associations were found between lower Aβ-42 and parieto-occipital periventricular WMHs. Regression analyses demonstrated that lower Aβ-42 correlated with larger WMH volumes in the splenium of the corpus callosum and posterior thalamic radiation, also after controlling for markers of vascular disease. P-tau was not consistently related to WMH occurrence. Our findings indicate that cerebral amyloid burden is associated with WMHs located in specific posterior white matter regions, possibly reflecting region-specific effects of amyloid pathology on the white matter.

Keywords: Alzheimer's disease; Amyloid-beta; Cerebrospinal fluid; Lesion mapping; Magnetic resonance imaging; Tau; White matter hyperintensities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / metabolism*
  • Humans
  • Magnetic Resonance Imaging
  • Peptide Fragments / metabolism*
  • White Matter / diagnostic imaging*
  • White Matter / metabolism*
  • White Matter / pathology
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins