Characterization of dural sinus-associated lymphatic vasculature in human Alzheimer's dementia subjects

Brain Behav Immun. 2018 Oct;73:34-40. doi: 10.1016/j.bbi.2018.07.020. Epub 2018 Jul 25.

Abstract

Recent reports describing lymphatic vasculature in the meninges have challenged the traditional understanding of interstitial solute clearance from the central nervous system, although the significance of this finding in human neurological disease remains unclear. To begin to define the role of meningeal lymphatic function in the clearance of interstitial amyloid beta (Aβ), and the contribution that its failure may make to the development of Alzheimer's disease (AD), we examined meningeal tissue from a case series including AD and control subjects by confocal microscopy. Our findings confirm the presence of lymphatic vasculature in the human meninges and indicate that, unlike perivascular efflux pathways in the brain parenchyma in subjects with AD, Aβ is not deposited in or around meningeal lymphatic vessels associated with dural sinuses. Our findings demonstrate that while the meningeal lymphatic vasculature may serve as an efflux route for Aβ from the brain and cerebrospinal fluid, Aβ does not deposit in the walls of meningeal lymphatic vessels in the setting of AD.

Keywords: Alzheimer’s disease; Amyloid beta; LYVE-1; Lymphatic; Meninges; Podoplanin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Brain / metabolism
  • Female
  • Glymphatic System / metabolism*
  • Glymphatic System / physiology
  • Humans
  • Lymphatic Vessels / metabolism
  • Lymphatic Vessels / physiology
  • Male
  • Membrane Glycoproteins / metabolism
  • Meninges / metabolism
  • Microscopy, Confocal / methods
  • Middle Aged
  • Nervous System Diseases / metabolism

Substances

  • Amyloid beta-Peptides
  • Membrane Glycoproteins
  • PDPN protein, human