An Integrated View on Vascular Dysfunction in Alzheimer’s Disease
Open accessAbstract
Background: Cerebrovascular disease is a common comorbidity in patients with Alzheimer’s disease (AD). It is believed to contribute additively to the cognitive impairment and to lower the threshold for the development of dementia. However, accumulating evidence suggests that dysfunction of the cerebral vasculature and AD neuropathology interact in multiple ways. Vascular processes even proceed AD neuropathology, implicating a causal role in the etiology of AD. Thus, the review aims to provide an integrated view on vascular dysfunction in AD. Summary: In AD, the cerebral vasculature undergoes pronounced cellular, morphological and structural changes, which alters regulation of blood flow, vascular fluid dynamics and vessel integrity. Stiffening of central blood vessels lead to transmission of excessive pulsatile energy to the brain microvasculature, causing end-organ damage. Moreover, a dysregulated hemostasis and chronic vascular inflammation further impede vascular function, where its mediators interact synergistically. Changes of the cerebral vasculature are triggered and driven by systemic vascular abnormalities that are part of aging, and which can be accelerated and aggravated by cardiovascular diseases. Key Messages: In AD, the cerebral vasculature is the locus where multiple pathogenic processes converge and contribute to cognitive impairment. Understanding the molecular mechanism and pathophysiology of vascular dysfunction in AD and use of vascular blood-based and imaging biomarker in clinical studies may hold promise for future prevention and therapy of the disease.
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Infectious triggers and neurovascular dysfunction have been proposed as additional contributors to AD.
“More recently, infectious triggers [18, 19] and neurovascular dysfunction [20] have been proposed as additional contributors, broadening the scope of investigation and linking AD to systemic physiology.”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [20]
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- Authors
- Klohs, J.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Klohs, Jan
- ORCID
- Klohs, Jan
- Venue
- Neurodegenerative Diseases
- Publisher
- S. Karger AG
- Published
- 2019
- Volume
- 19
- Issue
- 3-4
- Pages
- 109-127
- ISSN
- 1660-2854 (ISSN-L)
- 1660-2862
- OpenAlex
- W3005672607
- Cited by
- 111
- References
- 32
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 16 · 2023: 17 · 2022: 22 · 2021: 22 · 2020: 7
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurodegenerative Diseases (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc-nd)
- ETH Zürich Research Collection
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (32NE30_173678/1, 179277)
- Eidgenössische Technische Hochschule Zürich
- Universität Zürich
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, vascular dysfunction, cerebrovascular disease, cerebral microvasculature, blood flow regulation, vascular stiffness, pulsatile blood flow, hemostasis, vascular inflammation, aging, cardiovascular disease, cognitive impairment, imaging biomarkers, blood-based biomarkers
- MeSH terms
- Alzheimer Disease, Cerebrovascular Disorders, Humans
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