ArticleBrain pathology (Zurich, Switzerland)2020
Distinct changes in all major components of the neurovascular unit across different neuropathological stages of Alzheimer's disease.
Article in Brain pathology (Zurich, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
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- The crosstalk between blood-brain barrier and neural cells: bidirectional regulation of brain function and pathology.Biochemistry and biophysics reports · 2026Review
- Differential pericyte pathology in the human retina and brain in diabetes mellitus and Alzheimer's disease.Frontiers in neuroscience · 2026Article
- Border-associated macrophages: an emerging perspective from physiological basis and multi-disease roles to the mechanism of vascular cognitive impairment and dementia.Journal of neuroinflammation · 2025Review
- Brain pericytes derived from human pluripotent stem cells retain vascular and phagocytic functions under hypoxia.Stem cells (Dayton, Ohio) · 2025Article
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- Traumatic Brain Injury and Alzheimer's Disease: A Shared Neurovascular Hypothesis.Neuroscience insights · 2025Review
- Exercise-mediated cerebrovascular repair in Alzheimer's disease: from pathophysiology to therapeutic precision.Frontiers in aging neuroscience · 2025Review
- Loss of Direct Vascular Contact to Astrocytes in the Hippocampus as an Initial Event in Alzheimer's Disease. Evidence from Patients, In Vivo and In Vitro Experimental Models.Molecular neurobiology · 2024Article
- Development of capillary dysfunction in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- Integrative Transcriptomic Analyses of Hippocampal-Entorhinal System Subfields Identify Key Regulators in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Microglia and the Blood-Brain Barrier: An External Player in Acute and Chronic Neuroinflammatory Conditions.International journal of molecular sciences · 2023Review
- Microglia-Mediated Neurovascular Unit Dysfunction in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- Cooperation between neurovascular dysfunction and Aβ in Alzheimer's disease.Frontiers in molecular neuroscience · 2023Review
- Neuroprotection and Non-Invasive Brain Stimulation: Facts or Fiction?International journal of molecular sciences · 2022Review
- Astrocytes as a Therapeutic Target in Alzheimer's Disease-Comprehensive Review and Recent Developments.International journal of molecular sciences · 2022Review
- Evidence of beta amyloid independent small vessel disease in familial Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2022Article
- Pathological changes within the cerebral vasculature in Alzheimer's disease: New perspectives.Brain pathology (Zurich, Switzerland) · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In the brain capillaries, endothelial cells, pericytes, astrocytes and microglia form a structural and functional complex called neurovascular unit (NVU) which is critically involved in maintaining neuronal homeostasis. In the present study, we applied a comprehensive immunohistochemical approach to investigate the structural alterations in the NVU across different Alzheimer's disease (AD) neuropathological stages. Post-mortem human cortical and hippocampal samples derived from AD patients and non-demented elderly control individuals were immunostained using a panel of markers representing specific components of the NVU including Collagen IV (basement membrane), PDGFR-β (pericytes), GFAP (astrocytes), Iba1 (microglia), MRC1 (perivascular macrophages) and lectin as an endothelial cell label. Astrocytes (GFAP) and microglia (Iba1) were quantified both in the whole visual-field and specifically within the NVU, and the sample set was additionally analyzed using anti-tau (AT8) and three different anti-Aβ (clones G2-10, G2-11, 4G8) antibodies. Analyses of lectin labeled sections showed an altered vascular distribution in AD patients as revealed by a reduced nearest distance between capillaries. Within the NVU, a Braak-stage dependent reduction in pericyte coverage was identified as the earliest structural alteration during AD progression. In comparison to non-demented elderly controls, AD patients showed a significantly higher astrocyte coverage within the NVU, which was paralleled by a reduced microglial coverage around capillaries. Assessment of perivascular macrophages moreover demonstrated a relocation of these cells from leptomeningeal arteries to penetrating parenchymal vessels in AD patients. Collectively, the results of our study represent a comprehensive first in-depth analysis of AD-related structural changes in the NVU and suggest distinct alterations in all components of the NVU during AD progression.
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Registered trials
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