Diffuse white matter loss in a transgenic rat model of cerebral amyloid angiopathy.

Journal Article (Journal Article)

Diffuse white matter (WM) disease is highly prevalent in elderly with cerebral small vessel disease (cSVD). In humans, cSVD such as cerebral amyloid angiopathy (CAA) often coexists with Alzheimer's disease imposing a significant impediment for characterizing their distinct effects on WM. Here we studied the burden of age-related CAA pathology on WM disease in a novel transgenic rat model of CAA type 1 (rTg-DI). A cohort of rTg-DI and wild-type rats was scanned longitudinally using MRI for characterization of morphometry, cerebral microbleeds (CMB) and WM integrity. In rTg-DI rats, a distinct pattern of WM loss was observed at 9 M and 11 M. MRI also revealed manifestation of small CMB in thalamus at 6 M, which preceded WM loss and progressively enlarged until the moribund disease stage. Histology revealed myelin loss in the corpus callosum and thalamic CMB in all rTg-DI rats, the latter of which manifested in close proximity to occluded and calcified microvessels. The quantitation of CAA load in rTg-DI rats revealed that the most extensive microvascular Aβ deposition occurred in the thalamus. For the first time using in vivo MRI, we show that CAA type 1 pathology alone is associated with a distinct pattern of WM loss.

Full Text

Duke Authors

Cited Authors

  • Lee, H; Xu, F; Liu, X; Koundal, S; Zhu, X; Davis, J; Yanez, D; Schrader, J; Stanisavljevic, A; Rothman, DL; Wardlaw, J; Van Nostrand, WE; Benveniste, H

Published Date

  • May 1, 2021

Published In

Volume / Issue

  • 41 / 5

Start / End Page

  • 1103 - 1118

PubMed ID

  • 32791876

Pubmed Central ID

  • PMC8054716

Electronic International Standard Serial Number (EISSN)

  • 1559-7016

Digital Object Identifier (DOI)

  • 10.1177/0271678X20944226


  • eng

Conference Location

  • United States