Lead Acetate Exposure and Cerebral Amyloid Accumulation: Mechanistic Evaluations in APP/PS1 Mice.


Journal

Environmental health perspectives
ISSN: 1552-9924
Titre abrégé: Environ Health Perspect
Pays: United States
ID NLM: 0330411

Informations de publication

Date de publication:
Oct 2024
Historique:
medline: 16 10 2024
pubmed: 16 10 2024
entrez: 16 10 2024
Statut: ppublish

Résumé

The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model. Female APP/PS1 mice at 8 wk of age were administered either APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384.

Sections du résumé

BACKGROUND UNASSIGNED
The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain
OBJECTIVES UNASSIGNED
This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model.
METHODS UNASSIGNED
Female APP/PS1 mice at 8 wk of age were administered either
RESULTS UNASSIGNED
APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to
DISCUSSION UNASSIGNED
Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384.

Identifiants

pubmed: 39412896
doi: 10.1289/EHP14384
doi:

Substances chimiques

lead acetate RX077P88RY
Amyloid beta-Peptides 0
Organometallic Compounds 0
Amyloid beta-Protein Precursor 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

107004

Auteurs

Huiying Gu (H)

Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Luqing L Liu (LL)

School of Health Sciences, Purdue University, West Lafayette, Indiana, USA.

Alanna Wu (A)

Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Yongqi Yu (Y)

Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Uzay Emir (U)

School of Health Sciences, Purdue University, West Lafayette, Indiana, USA.

Stephen J Sawiak (SJ)

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Department of Psychology, University of Cambridge, Cambridge, UK.

Paul R Territo (PR)

Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Matin R Farlow (MR)

Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Wei Zheng (W)

School of Health Sciences, Purdue University, West Lafayette, Indiana, USA.

Yansheng Du (Y)

Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.

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Classifications MeSH