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

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          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.

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          Author and article information

          Journal
          8800478
          1990
          Brain Behav Immun
          Brain Behav. Immun.
          Brain, behavior, and immunity
          0889-1591
          1090-2139
          8 August 2018
          25 July 2018
          October 2018
          01 October 2019
          : 73
          : 34-40
          Affiliations
          [1 ]Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
          [2 ]Department of Physiology and Pharmacology, Oregon Health & Science University, Portland, OR, USA.
          [3 ]Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
          [4 ]Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
          [5 ]Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
          [6 ]Knight Cardiovascular Research Institute; Oregon Health & Science University, Portland, OR, USA.
          Author notes

          Author Contributions

          JRG, ZOA, AWL, and JJI wrote the manuscript. JRG and ZOA performed immunofluorescence, acquisition, and post-image processing. Data analysis was performed by JRG, ZOA, AWL, RLW, and JJI. Study design was planned by JRG, RLW, and JJI.

          [* ] Corresponding Author: Jeffrey J. Iliff, PhD, Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Mail Code L459 Portland, OR 97239 USA, iliffj@ 123456ohsu.edu , Phone: (503) 494-4047
          Article
          PMC6149215 PMC6149215 6149215 nihpa1503059
          10.1016/j.bbi.2018.07.020
          6149215
          30055243
          Categories
          Article

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