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Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease

Vascular dysfunction and structural abnormalities in Alzheimer’s disease (AD) are known to contribute to the progression of the pathology, and studies have tended to ignore the role of the vasculature in AD progression. We utilized the 3xTg-AD mouse model of AD to examine individual cerebral vessels...

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Autores principales: Jullienne, Amandine, Quan, Ryan, Szu, Jenny I., Trinh, Michelle V., Behringer, Erik J., Obenaus, Andre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405684/
https://www.ncbi.nlm.nih.gov/pubmed/36009514
http://dx.doi.org/10.3390/biomedicines10081967
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author Jullienne, Amandine
Quan, Ryan
Szu, Jenny I.
Trinh, Michelle V.
Behringer, Erik J.
Obenaus, Andre
author_facet Jullienne, Amandine
Quan, Ryan
Szu, Jenny I.
Trinh, Michelle V.
Behringer, Erik J.
Obenaus, Andre
author_sort Jullienne, Amandine
collection PubMed
description Vascular dysfunction and structural abnormalities in Alzheimer’s disease (AD) are known to contribute to the progression of the pathology, and studies have tended to ignore the role of the vasculature in AD progression. We utilized the 3xTg-AD mouse model of AD to examine individual cerebral vessels and the cortical vascular network across the lifespan. Our vessel painting approach was used to label the entire cortical vasculature, followed by epifluorescence microscopy. The middle cerebral artery (MCA) tree was assessed with confocal microscopy, and a new method was developed to assess branching patterns as a measure of aging-related changes. We found that vascular remodeling was profoundly altered at 4–6 months of age, when the 3xTg-AD mouse is known to transition to cognitive impairment and Aβ deposition in both sexes. Analysis of vascular features (density, junctions, length) of the MCA territory highlighted sex-dependent differences across the 3xTg-AD mouse lifespan, with no alterations in branching patterns. Our current cerebrovascular angioarchitectural analyses demonstrate progressive alterations in individual cortical vessels, as well as in the vascular network of the cortex. These new findings advance our understanding of brain anatomy and physiology in the 3xTg-AD mouse, while potentially identifying unique diagnostic signatures of AD progression.
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spelling pubmed-94056842022-08-26 Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease Jullienne, Amandine Quan, Ryan Szu, Jenny I. Trinh, Michelle V. Behringer, Erik J. Obenaus, Andre Biomedicines Article Vascular dysfunction and structural abnormalities in Alzheimer’s disease (AD) are known to contribute to the progression of the pathology, and studies have tended to ignore the role of the vasculature in AD progression. We utilized the 3xTg-AD mouse model of AD to examine individual cerebral vessels and the cortical vascular network across the lifespan. Our vessel painting approach was used to label the entire cortical vasculature, followed by epifluorescence microscopy. The middle cerebral artery (MCA) tree was assessed with confocal microscopy, and a new method was developed to assess branching patterns as a measure of aging-related changes. We found that vascular remodeling was profoundly altered at 4–6 months of age, when the 3xTg-AD mouse is known to transition to cognitive impairment and Aβ deposition in both sexes. Analysis of vascular features (density, junctions, length) of the MCA territory highlighted sex-dependent differences across the 3xTg-AD mouse lifespan, with no alterations in branching patterns. Our current cerebrovascular angioarchitectural analyses demonstrate progressive alterations in individual cortical vessels, as well as in the vascular network of the cortex. These new findings advance our understanding of brain anatomy and physiology in the 3xTg-AD mouse, while potentially identifying unique diagnostic signatures of AD progression. MDPI 2022-08-13 /pmc/articles/PMC9405684/ /pubmed/36009514 http://dx.doi.org/10.3390/biomedicines10081967 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jullienne, Amandine
Quan, Ryan
Szu, Jenny I.
Trinh, Michelle V.
Behringer, Erik J.
Obenaus, Andre
Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease
title Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease
title_full Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease
title_fullStr Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease
title_full_unstemmed Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease
title_short Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease
title_sort progressive vascular abnormalities in the aging 3xtg-ad mouse model of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405684/
https://www.ncbi.nlm.nih.gov/pubmed/36009514
http://dx.doi.org/10.3390/biomedicines10081967
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