Age-associated Physiological and Pathological Changes at the Blood-Brain Barrier: A Review

Erdő, Franciska; Denes, László; de Lange, Elizabeth

doi:10.1177/0271678x16679420

Cited by 426Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsCerebrospinal fluid and hydrocephalus

Age-associated Physiological and Pathological Changes at the Blood-Brain Barrier: A Review

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Erdő, Franciska, Denes, László, de Lange, Elizabeth·2017·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1177/0271678x16679420PMC PMC5363756

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Abstract

The age-associated decline of the neurological and cognitive functions becomes more and more serious challenge for the developed countries with the increasing number of aged populations. The morphological and biochemical changes in the aging brain are the subjects of many extended research projects worldwide for a long time. However, the crucial role of the blood-brain barrier (BBB) impairment and disruption in the pathological processes in age-associated neurodegenerative disorders received special attention just for a few years. This article gives an overview on the major elements of the blood-brain barrier and its supporting mechanisms and also on their alterations during development, physiological aging process and age-associated neurodegenerative disorders (Alzheimer's disease, multiple sclerosis, Parkinson's disease, pharmacoresistant epilepsy). Besides the morphological alterations of the cellular elements (endothelial cells, astrocytes, pericytes, microglia, neuronal elements) of the BBB and neurovascular unit, the changes of the barrier at molecular level (tight junction proteins, adheres junction proteins, membrane transporters, basal lamina, extracellular matrix) are also summarized. The recognition of new players and initiators of the process of neurodegeneration at the level of the BBB may offer new avenues for novel therapeutic approaches for the treatment of numerous chronic neurodegenerative disorders currently without effective medication.

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Normal physiological aging is associated with BBB disruption through multiple mechanisms including decreased expression of endothelial tight junction proteins, increased microglial activation, and neuronal senescence.
“Normal physiological aging is associated with BBB disruption through multiple mechanisms including decreased expression of endothelial tight junction proteins, increased microglial activation, and neuronal senescence (Erdő et al., 2017).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Erdő et al., 2017
Many neurological conditions confer heightened damage by PFAS and other toxicants by functionally compromising the BBB.
“Many neurological conditions, including Alzheimer’s disease (AD), Parkinson’s Disease (PD), multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), Huntington’s disease, and brain tumors, confer heightened damage by PFAS and other toxicants by functionally compromising the BBB”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Erdő et al., 2017

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Authors: Erdő, F., Denes, L., & de Lange, E.
Affiliations: Pázmány Péter Catholic University (HU)
Institute of Pharmacology & Pharmacotherapy, Semmelweis University, Budapest, Hungary
Gorlaeus Laboratories, Leiden University, Leiden, The Netherlands
Corresponding author: Erdő, Franciska
ORCID: Erdő, Franciska
Venue: Journal of Cerebral Blood Flow & Metabolism
Publisher: SAGE Publications
Published: 2016-11-13
Volume: 37
Issue: 1
Pages: 4-24
ISSN: 0271-678X (ISSN-L)
1559-7016
DOI: 10.1177/0271678x16679420
PMC: PMC5363756
OpenAlex: W2555740579
Cited by: 426
References: 169
Citations by year: 2026: 21 · 2025: 41 · 2024: 36 · 2023: 39 · 2022: 57 · 2021: 65 · 2020: 58 · 2019: 43 · 2018: 40 · 2017: 25 · 2016: 1
FWCI: 3.18
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Leiden Repository (Leiden University) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords: blood-brain barrier, aging, Alzheimer's disease, multiple sclerosis, Parkinson's disease, drug-resistant epilepsy, tight junction proteins, adherens junction proteins, membrane transporters, basement membrane, extracellular matrix, neurovascular unit, endothelial cells, astrocytes, pericytes, microglia, cognitive decline
MeSH terms: Aging, Blood-Brain Barrier, Humans, Neurodegenerative Diseases

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Age-associated Physiological and Pathological Changes at the Blood-Brain Barrier: A Review

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