Vascular dysfunction occurs prior to the onset of amyloid pathology and Aβ plaque deposits colocalize with endothelial cells in the hippocampus of female APPswe/PSEN1dE9 mice.
APPswe/PSEN1dE9 mice
Alzheimer’s disease
Amyloid β1-42
Vascular dysfunction
Vascular stiffness
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
11 Jun 2024
11 Jun 2024
Historique:
received:
25
03
2024
accepted:
18
05
2024
medline:
12
6
2024
pubmed:
12
6
2024
entrez:
11
6
2024
Statut:
aheadofprint
Résumé
Increasing evidence shows that cardiovascular diseases (CVDs) are associated with an increased risk of cognitive impairment and Alzheimer's diseases (AD). It is unknown whether systemic vascular dysfunction occurs prior to the development of AD, if this occurs in a sex-dependent manner, and whether endothelial cells play a role in the deposition of amyloid beta (Aβ) peptides. We hypothesized that vascular dysfunction occurs prior to the onset of amyloid pathology, thus escalating its progression. Furthermore, endothelial cells from female mice will present with an exacerbated formation of Aβ peptides due to an exacerbated pressure pulsatility. To test this hypothesis, we used a double transgenic mouse model of early-onset AD (APPswe/PSEN1dE9). We evaluated hippocampus-dependent recognition memory and the cardiovascular function by echocardiography and direct measurements of blood pressure through carotid artery catheterization. Vascular function was evaluated in resistance arteries, morphometric parameters in the aortas, and immunofluorescence in the hippocampus and aortas. We observed that endothelial dysfunction occurred prior to the onset of amyloid pathology irrespective of sex. However, during the onset of amyloid pathology, only female APP/PS1 mice had vascular stiffness in the aorta. There was elevated Aβ deposition which colocalized with endothelial cells in the hippocampus from female APP/PS1 mice. Overall, these data showed that vascular abnormalities may be an early marker, and potential mediator of AD, but exacerbated aortic stiffness and pressure pulsatility after the onset of amyloid pathology may be associated with a greater burden of Aβ formation in hippocampal endothelial cells from female but not male APP/PS1 mice.
Identifiants
pubmed: 38862757
doi: 10.1007/s11357-024-01213-0
pii: 10.1007/s11357-024-01213-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : R01HL149762
Pays : United States
Organisme : NIH HHS
ID : R00HL151889
Pays : United States
Organisme : NIH HHS
ID : P20GM103641
Pays : United States
Organisme : National Institute of Health
ID : DK132948
Organisme : Alzheimer's Association
ID : AARG-NTF-23-1145090
Pays : United States
Informations de copyright
© 2024. The Author(s).
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