Association of Perivascular Localization of Aquaporin-4 With Cognition and Alzheimer Disease in Aging Brains DOI
Douglas Zeppenfeld, Matthew Simon,

John Douglas Haswell

et al.

JAMA Neurology, Journal Year: 2016, Volume and Issue: 74(1), P. 91 - 91

Published: Nov. 28, 2016

Importance

Cognitive impairment and dementia, including Alzheimer disease (AD), are common within the aging population, yet factors that render brain vulnerable to these processes unknown. Perivascular localization of aquaporin-4 (AQP4) facilitates clearance interstitial solutes, amyloid-β, through brainwide network perivascular pathways termed theglymphatic system, which may be compromised in brain.

Objectives

To determine whether alterations AQP4 expression or loss features human define their association with AD pathology.

Design, Setting, Participants

Expression was analyzed postmortem frontal cortex cognitively healthy histopathologically confirmed individuals by Western blot immunofluorescence for AQP4, amyloid-β 1-42, glial fibrillary acidic protein. Postmortem tissue clinical data were provided Oregon Health Science University Layton Aging Disease Center Brain Bank. from 79 evaluated, intact “young” aged younger than 60 years (range, 33-57 years), “aged” older 61-96 years) no known neurological disease, 61-105 age a history histopathological evaluation. Forty-eight patient samples (10 young, 20 aged, 18 AD) underwent histological analysis. Sixty analysis (15 24 21 AD).

Main Outcomes Measures

protein, immunoreactivity, evaluated.

Results

associated advancing among all (R2 = 0.17;P .003). significantly status independent (OR, 11.7 per 10% increase localization; z −2.89;P .004) preserved eldest 85 who remained intact. When controlling age, increased burden 0.15;P .003) increasing Braak stage 0.14;P .006).

Conclusions Relevance

In this study, altered brains. Loss factor renders misaggregation proteins, such as neurodegenerative conditions AD.

Language: Английский

Regulation of cerebral blood flow in humans: physiology and clinical implications of autoregulation DOI
Jurgen A.H.R. Claassen, Dick H. J. Thijssen, Ronney B. Panerai

et al.

Physiological Reviews, Journal Year: 2021, Volume and Issue: 101(4), P. 1487 - 1559

Published: March 26, 2021

Brain function critically depends on a close matching between metabolic demands, appropriate delivery of oxygen and nutrients, removal cellular waste. This requires continuous regulation cerebral blood flow (CBF), which can be categorized into four broad topics:

Language: Английский

Citations

548
Understanding the functions and relationships of the glymphatic system and meningeal lymphatics DOI Open Access
Antoine Louveau,

Benjamin A. Plog,

Salli Antila

et al.

Journal of Clinical Investigation, Journal Year: 2017, Volume and Issue: 127(9), P. 3210 - 3219

Published: Aug. 31, 2017

Recent discoveries of the glymphatic system and meningeal lymphatic vessels have generated a lot excitement, along with some degree skepticism. Here, we summarize state field point out gaps knowledge that should be filled through further research. We discuss as allows CNS perfusion by cerebrospinal fluid (CSF) interstitial (ISF). also describe recently characterized their role in drainage brain ISF, CSF, CNS-derived molecules, immune cells from meninges to peripheral (CNS-draining) lymph nodes. speculate on relationship between two systems malfunction may underlie neurological diseases. Although much remains investigated, these new changed our understanding mechanisms underlying privilege drainage. Future studies explore communications lymphatics disorders develop therapeutic modalities targeting systems.

Language: Английский

Citations

542
The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease DOI Creative Commons
Guillermo Oliver, Jonathan Kipnis, Gwendalyn J. Randolph

et al.

Cell, Journal Year: 2020, Volume and Issue: 182(2), P. 270 - 296

Published: July 1, 2020

Language: Английский

Citations

515
Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease DOI Creative Commons
Amy R. Nelson, Melanie D. Sweeney, Abhay P. Sagare

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2015, Volume and Issue: 1862(5), P. 887 - 900

Published: Dec. 18, 2015

Language: Английский

Citations

489
Association of Perivascular Localization of Aquaporin-4 With Cognition and Alzheimer Disease in Aging Brains DOI
Douglas Zeppenfeld, Matthew Simon,

John Douglas Haswell

et al.

JAMA Neurology, Journal Year: 2016, Volume and Issue: 74(1), P. 91 - 91

Published: Nov. 28, 2016

Importance

Cognitive impairment and dementia, including Alzheimer disease (AD), are common within the aging population, yet factors that render brain vulnerable to these processes unknown. Perivascular localization of aquaporin-4 (AQP4) facilitates clearance interstitial solutes, amyloid-β, through brainwide network perivascular pathways termed theglymphatic system, which may be compromised in brain.

Objectives

To determine whether alterations AQP4 expression or loss features human define their association with AD pathology.

Design, Setting, Participants

Expression was analyzed postmortem frontal cortex cognitively healthy histopathologically confirmed individuals by Western blot immunofluorescence for AQP4, amyloid-β 1-42, glial fibrillary acidic protein. Postmortem tissue clinical data were provided Oregon Health Science University Layton Aging Disease Center Brain Bank. from 79 evaluated, intact “young” aged younger than 60 years (range, 33-57 years), “aged” older 61-96 years) no known neurological disease, 61-105 age a history histopathological evaluation. Forty-eight patient samples (10 young, 20 aged, 18 AD) underwent histological analysis. Sixty analysis (15 24 21 AD).

Main Outcomes Measures

protein, immunoreactivity, evaluated.

Results

associated advancing among all (R2 = 0.17;P .003). significantly status independent (OR, 11.7 per 10% increase localization; z −2.89;P .004) preserved eldest 85 who remained intact. When controlling age, increased burden 0.15;P .003) increasing Braak stage 0.14;P .006).

Conclusions Relevance

In this study, altered brains. Loss factor renders misaggregation proteins, such as neurodegenerative conditions AD.

Language: Английский

Citations

472