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

James R. Goodman, Zachariah O. Adham, Randall (Randy) Woltjer, Amanda Lund, Jeffrey Iliff

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
JournalBrain, Behavior, and Immunity
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Alzheimer Disease
Meninges
Lymphatic Vessels
Brain
Amyloid
Confocal Microscopy
Cerebrospinal Fluid
Central Nervous System

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Lymphatic
  • LYVE-1
  • Meninges
  • Podoplanin

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

@article{ad838ef3512c439399a154676156874c,
title = "Characterization of dural sinus-associated lymphatic vasculature in human Alzheimer's dementia subjects",
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, Lymphatic, LYVE-1, Meninges, Podoplanin",
author = "Goodman, {James R.} and Adham, {Zachariah O.} and Woltjer, {Randall (Randy)} and Amanda Lund and Jeffrey Iliff",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.bbi.2018.07.020",
language = "English (US)",
journal = "Brain, Behavior, and Immunity",
issn = "0889-1591",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Characterization of dural sinus-associated lymphatic vasculature in human Alzheimer's dementia subjects

AU - Goodman, James R.

AU - Adham, Zachariah O.

AU - Woltjer, Randall (Randy)

AU - Lund, Amanda

AU - Iliff, Jeffrey

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Amyloid beta

KW - Lymphatic

KW - LYVE-1

KW - Meninges

KW - Podoplanin

UR - http://www.scopus.com/inward/record.url?scp=85050659891&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050659891&partnerID=8YFLogxK

U2 - 10.1016/j.bbi.2018.07.020

DO - 10.1016/j.bbi.2018.07.020

M3 - Article

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

SN - 0889-1591

ER -