Bacille Calmette-Guérin attenuates vascular amyloid pathology and maximizes synaptic preservation in APP/PS1 mice following active amyloid-β immunotherapy

Zuo, Zejie; Qi, Fangfang; Xing, Zhimin; Yuan, Lifang; Yang, Yong; He, Zitian; Zhou, Lihua; Ye, Zhibin

doi:10.1016/j.neurobiolaging.2021.01.001

Cited by 10 publications

(7 citation statements)

References 75 publications

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“…It was consistent with the reported results that APP could mediate the production of Aβ and affect the density of brain perivascular macrophages in the vasculature of the hippocampus ( Karam et al, 2022 ). A previous study found that the recruited macrophages could enhance the vascular Aβ phagocytosis for immunotherapy in APP/PS1 mice ( Zuo et al, 2021 ). In addition, the deposition of vascular Aβ in the cerebral vasculature could cause breakdown of the vascular integrity and a decrease in the number of cerebrovascular endothelial cells and pericytes ( Sweeney et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease

Xu,

Zhang,

Tang

et al. 2024

Front. Cell Dev. Biol.

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Introduction: The incidence of diabetic retinopathy (DR) has been found to be associated with the risk of developing Alzheimer‘s disease (AD). In addition to the common properties of neurodegeneration, their progressions are involved with abnormal vascular functions. However, the interactions between them have not been fully understood. This study aimed to investigate the key factor for the underlying interactions and shared signaling pathways in the vasculature of DR and AD.Methods: We retrieved single-cell RNA sequencing (scRNA-seq) data regarding human fibrovascular membrane (FVM) of proliferative diabetic retinopathy (PDR) and human hippocampus vessels of AD from the NCBI-GEO database. GSEA analysis was performed to analyze AD-related genes in endothelial cells and pericytes of PDR. CellChat was used for predicting cell-cell communication and the signaling pathway.Results: The data suggested that amyloid-beta precursor protein (APP) signaling was found crucial in the vasculature of PDR and AD. Endothelial cells and pericytes could pose influences on other cells mainly via APP signaling in PDR. The endothelial cells were mainly coordinated with macrophages in the hippocampus vasculature of AD via APP signaling. The bulk RNA-seq in mice with PDR validated that the expression of APP gene had a significant correlation with that of the AD genome-wide association studies (GWAS) gene.Discussion: Our study demonstrates that the vasculopathy of PDR and AD is likely to share a common signaling pathway, of which the APP-related pathway is a potential target.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease

Xu,

Zhang,

Tang

et al. 2024

Front. Cell Dev. Biol.

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“…Furthermore, animal studies in mice have shown that infections such as influenza have been shown to cause neuroinflammation resulting in long-term neurological sequelae, which can be prevented by vaccination. 49,50 This provides another potential link between vaccinations and reduced inflammation and neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

“…Vaccines have been shown to non-specifically activate Toll-like receptors leading to an increase in microglial/macrophage activity reducing neuroinflammation, and two studies with BCG vaccination in APP/PS1 mice have shown that BCG vaccination improves cognition and reduces neuroinflammation. 49 Vaccines may therefore reduce the risk of dementia through activation of regulatory T cells, 51 training the immune system, 24 increasing microglial/macrophage activity, 52 and reduction of chronic inflammation, as well as reducing incidence of infections associated with dementia. 34 This evidence provides a necessary connection between the related roles of inflammation and immune function in dementia and Alzheimer's risk.…”

Section: Discussionmentioning

confidence: 99%

Could routine vaccinations prevent dementia?

Poynton-Smith

Orrell

Morley

et al. 2023

Int J Geriat Psychiatry

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“… 7–9 Our research group previously observed that BCG improves cognitive impairment in APP/PS1 mice and reduces the neuroinflammatory responses, suggesting the existence of an altered cytokine dynamic that possibly impacts the dendritic morphology in the hippocampus. 10 , 11 Hence, in this study, we analyzed the dendrites complexity of hippocampal pyramidal neurons following immunization of APP/PS1 mice with BCG. It is worth noting that, APP/PS1 mice showed cognitive decline from the age of 6 months, however, hippocampal mossy fiber synapses display morphological and functional presynaptic deficits in middle-aged mice (3 to 6 months).…”

Section: Discussionmentioning

confidence: 99%

“…Alzheimer’s disease (AD) is a neurodegenerative disease, and immunotherapy has been identified as an important direction for clinical treatment. The use of BCG in APP/PS1 mice has been reported; 10 , 11 however, the specific mechanism for the neuroprotective effect of BCG on synaptic damage remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Changes in dendritic complexity and spine morphology following BCG immunization in APP/PS1 mice

Li¹,

Wang²,

Wang³

et al. 2022

Human Vaccines & Immunotherapeutics

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Bacillus Calmette – Guerin (BCG) is an immune regulator that can enhance hippocampal synaptic plasticity in rats; however, it is unclear whether it can improve synaptic function in a mouse model with Alzheimer’s disease (AD). We hypothesized that BCG plays a protective role in AD mice and investigated its effect on dendritic morphology. The results obtained show that BCG immunization significantly increases dendritic complexity, as indicated by the increased number of dendritic intersections and branch points, as well as the increase in the fractal dimension. Furthermore, the number of primary neurites and dendritic length also increased following BCG immunization, which increased the number of spines and promoted maturation. IFN-γ and IL-4 levels increased, while TNF-α levels decreased following BCG immunization; expression levels of p -JAK2, P-STAT3, SYN, and PSD-95 also increased. Therefore, this study demonstrates that BCG immunization in APP/PS1 mice mitigated hippocampal dendritic spine pathology, especially after the third round of immunization. This effect could possibly be attributed to; changes in dendritic arborization and spine morphology or increases in SYN and PSD-95 expression levels. It could also be related to mechanisms of BCG-induced increases in IFN-γ or IL-4/JAK2/STAT3 levels.

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Bacille Calmette-Guérin attenuates vascular amyloid pathology and maximizes synaptic preservation in APP/PS1 mice following active amyloid-β immunotherapy

Cited by 10 publications

References 75 publications

Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease

Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer’s disease

Could routine vaccinations prevent dementia?

Changes in dendritic complexity and spine morphology following BCG immunization in APP/PS1 mice

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