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Cited by 451Barrier Structure and Function StudiesAlzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalus

Blood-Brain Barrier Dysfunction and the Pathogenesis of Alzheimer’s Disease

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Yamazaki, Yu, Kanekiyo, Takahisa·2017·International Journal of Molecular Sciences
DOI 10.3390/ijms18091965PMC PMC5618614
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Abstract

Brain capillary endothelial cells form the blood-brain barrier (BBB), which is covered with basement membranes and is also surrounded by pericytes and astrocyte end-feet in the neurovascular unit. The BBB tightly regulates the molecular exchange between the blood flow and brain parenchyma, thereby regulating the homeostasis of the central nervous system (CNS). Thus, dysfunction of the BBB is likely involved in the pathogenesis of several neurological diseases, including Alzheimer’s disease (AD). While amyloid-β (Aβ) deposition and neurofibrillary tangle formation in the brain are central pathological hallmarks in AD, cerebrovascular lesions and BBB alteration have also been shown to frequently coexist. Although further clinical studies should clarify whether BBB disruption is a specific feature of AD pathogenesis, increasing evidence indicates that each component of the neurovascular unit is significantly affected in the presence of AD-related pathologies in animal models and human patients. Conversely, since some portions of Aβ are eliminated along the neurovascular unit and across the BBB, disturbing the pathways may result in exacerbated Aβ accumulation in the brain. Thus, current evidence suggests that BBB dysfunction may causatively and consequently contribute to AD pathogenesis, forming a vicious cycle between brain Aβ accumulation and neurovascular unit impairments during disease progression.

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  • Post-mortem studies of Alzheimer's disease patients show extensive loss or delocalization of tight junction proteins in brain capillaries, strongly correlating with blood-brain barrier leakage.

    “Post-mortem studies of AD patients show extensive loss or delocalization of these proteins in brain capillaries, which strongly correlates with BBB leakage [53].”

    From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [53]

    Section 4.1 reports substantial loss of tight junction proteins in postmortem human brain capillaries with cerebral amyloid angiopathy, accompanied by increased fibrinogen leakage. It does not report delocalization or a strong correlation, and the finding is limited to capillaries with cerebral amyloid angiopathy rather than brain capillaries generally. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Yamazaki, Y., & Kanekiyo, T.
Affiliations
Mayo Clinic (US)
Corresponding author
Kanekiyo, Takahisa
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2017-09-13
Volume
18
Issue
9
Pages
1965
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms18091965
PMC
PMC5618614
OpenAlex
W2756319919
Cited by
451
References
27
Citations by year
2026: 31 · 2025: 54 · 2024: 40 · 2023: 54 · 2022: 65 · 2021: 66 · 2020: 55 · 2019: 35 · 2018: 32 · 2017: 2
FWCI
3.27
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (R01AG051574)
  • American Heart Association (15SDG22460003)
  • Florida Department of Health Ed and Ethel Moore Alzheimer’s Disease Research Program (7AZ22)
  • Japan Society for the Promotion of Science
  • Mochida Memorial Foundation for Medical & Pharmaceutical Research
  • Alzheimer’s Disease Research Center
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
Keywords
blood-brain barrier dysfunction, Alzheimer's disease pathogenesis, neurovascular unit, brain microvascular endothelial cells, pericytes, astrocyte endfeet, amyloid-beta deposition, cerebrovascular lesions, amyloid-beta clearance, neurofibrillary tangles
MeSH terms
Albumins, Alzheimer Disease, Animals, Astrocytes, Basement Membrane, Biological Transport, Blood-Brain Barrier, Brain, Central Nervous System, Cerebrovascular Disorders, Homeostasis, Humans, Peptide Fragments, Serum Albumin, Amyloid beta-Peptides, Cerebral Amyloid Angiopathy, Disease Progression, Tight Junctions, Pericytes, Endothelial Cells

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