ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Biomechanics
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1597917
This article is part of the Research TopicVascular Diseases of the Brain: Insights, Progress and Lessons LearnedView all 8 articles
CEREBROVASCULAR REMODELING IN AGING AND NEURODEGENERATIVE DISEASE PROGRESSION
Provisionally accepted
Samuel Halvorsen
Anastasia Gkousioudi
R Nicks
Victor Alvarez
Irving Bigio
Joseph Zaia
Thor Stein
Katherine Yanhang Zhang*- Boston University, Boston, United States
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The cerebrovasculature is responsible for supplying oxygenated blood and nutrients to the brain and removing neurotoxic buildup. With age, trauma, and disease, the structural constituents of cerebral arteries including the extracellular matrix and smooth muscle cells are subject to remodeling and degradation. Cerebrovascular dysfunction can have detrimental impacts on the brain and is closely associated with cognitive impairment. Clinical studies have found that cerebrovascular dysfunction is correlated with cognitive decline in neurodegenerative diseases including Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE). However, cerebrovascular changes during the progression of neurological disorders remain to be understood. Using matched and parallel studies of cerebrovasculature and brain tissue, this study set out to determine the temporal development of cerebrovascular remodeling and neurodegenerative disease progression. We examined changes to human anterior cerebral arteries (ACAs) from subjects with various degrees of AD and CTE neuropathology. Using biaxial inflation-extension testing, histological staining, and multiphoton imaging, we examined changes to the mechanical response and to the ACA wall structure. We found circumferential stiffening of the ACA with age. Furthermore, a minor relationship was reported between ACA stiffening and elevated levels of tau-based neuropathologies including neurofibrillary tangles, characteristic of both AD and CTE. Histological and multiphoton structural studies of the ACAs revealed smooth muscle cell atrophy at the media-adventitia interface and disorganization and straightening of adventitial collagen with age and disease. Our study reveals changes to the extracellular and cellular components of cerebral arteries that help describe the functional alterations of cerebrovasculature. Results from this study shed light on the complex relationship between cerebrovascular remodeling and neurodegenerative disease progression.
Keywords: Anterior cerebral artery (ACA), Alzhemer's disease, Chronic traumatic encephalopathies (CTE), Neuropathology, Mechanical characterization, Multiphoton imaging, Aging
Received: 21 Mar 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Halvorsen, Gkousioudi, Nicks, Alvarez, Bigio, Zaia, Stein and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Katherine Yanhang Zhang, Boston University, Boston, United States
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