<scp>5xFAD</scp> mice do not have myenteric amyloidosis, dysregulation of neuromuscular transmission or gastrointestinal dysmotility

Yelleswarapu, Narayana Krishna; Masino, Marlene; Henderson, Skye; Fernandes, Roxanne; Swain, Greg M.; Galligan, James J.; Xu, Hui

doi:10.1111/nmo.14439

Cited by 4 publications

(3 citation statements)

References 36 publications

(130 reference statements)

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“…By immunofluorescence (IF) staining, we found no Aβ in the 5XFAD colon (Fig. S2) as previously reported [47].…”

Section: Resultssupporting

confidence: 88%

Single-cell transcriptomics reveals colonic immune perturbations during amyloid-β driven Alzheimer’s disease in mice

Makhijani,

Emani,

Aguirre

et al. 2024

Preprint

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The "gut-brain axis" is emerging as an important target in Alzheimer's disease (AD). However, immunological mechanisms underlying this axis remain poorly understood. Using single-cell RNA sequencing of the colon immune compartment in the 5XFAD amyloid-β (Aβ) mouse model, we uncovered AD-associated changes in ribosomal activity, oxidative stress, and BCR/plasma cell activity. Strikingly, levels of colon CXCR4+ antibody secreting cells (ASCs) were significantly reduced. This corresponded with accumulating CXCR4+ B cells and gut-specific IgA+ cells in the brain and dura mater, respectively. Consistently, a chemokine ligand for CXCR4, CXCL12, was expressed at higher levels in 5XFAD glial cells and in in silico analyzed human brain studies, supporting altered neuroimmune trafficking. An inulin prebiotic fiber diet attenuated AD markers including Aβ plaques and overall frailty. These changes corresponded to an expansion of gut IgA+ cells and rescued peripheral Tregs levels. Our study points to a key glia-gut axis and potential targets against AD.

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“…By immunofluorescence (IF) staining, we found no Aβ in the 5XFAD colon (Fig. S2) as previously reported [47].…”

Section: Resultssupporting

confidence: 88%

Single-cell transcriptomics reveals colonic immune perturbations during amyloid-β driven Alzheimer’s disease in mice

Makhijani,

Emani,

Aguirre

et al. 2024

Preprint

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“…Additionally, both Aβ and phosphorylated tau protein were observed in the ENS neurons of the colon of AD patients. In contrast, Yelleswarapu et al could not detect Aβ accumulation in the colonic MP of 5xFAD mice and GI dysmotility at 6 months of age [132]. However, while using the 5xFAD mice, our own previous studies showed Aβ depositions in the muscular layer, as well as the MP and SP of the duodenum and ascending colon [130,133].…”

Section: Involvement Of the Ens In Alzheimer's Diseasecontrasting

confidence: 64%

The Aging Enteric Nervous System

Nguyen

Baumann

Tüscher

et al. 2023

IJMS

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The gut and the brain communicate via the nervous system, hormones, microbiota-mediated substances, and the immune system. These intricate interactions have led to the term “gut-brain axis”. Unlike the brain—which is somewhat protected—the gut is exposed to a variety of factors throughout life and, consequently, might be either more vulnerable or better adapted to respond to these challenges. Alterations in gut function are common in the elder population and associated with many human pathologies, including neurodegenerative diseases. Different studies suggest that changes in the nervous system of the gut, the enteric nervous system (ENS), during aging may result in gastrointestinal dysfunction and initiate human pathologies of the brain via its interconnection with the gut. This review aims at summarizing the contribution of normal cellular aging to the age-associated physiological changes of the ENS. Morphological alterations and degeneration of the aging ENS are observed in different animal models and humans, albeit with considerable variability. The aging phenotypes and pathophysiological mechanisms of the aging ENS have highlighted the involvement of enteric neurons in age-related diseases of the central nervous system such as Alzheimer’s or Parkinson’s disease. To further elucidate such mechanisms, the ENS constitutes a promising source of material for diagnosis and therapeutic predictions, as it is more accessible than the brain.

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“…The 5×FAD transgenic mouse line carries the Swedish ( KM670/671NL ), Florida ( I716V ), and London ( V717I ) mutations of APP and the M146L and L286V mutations of PSEN1 under the control of the Thy-1 promoter. These mice represent a robust model for studying amyloidosis, with abundant Aβ accumulation in the brain at 6 months and cognitive impairment detected at 4–6 months ( Oakley et al, 2006 ; Yelleswarapu et al, 2022 ). Triple Tg (3×Tg-AD) mice overexpress APP with the Swedish K670N/M671L mutation, PSEN1 with the M146V mutation, and protein tau with the P301L mutation, establishing a robust model for studying tau pathology and amyloidosis.…”

Section: Autophagy In Pathogenesis Of Ad Animal Modelsmentioning

confidence: 99%

Targeting autophagy in Alzheimer’s disease: Animal models and mechanisms

Zhang,

Zhu,

Tang

et al. 2023

Zoological Research

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Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder that leads to cognitive impairment and memory loss. Emerging evidence suggests that autophagy plays an important role in the pathogenesis of AD through the regulation of amyloid-beta (Aβ) and tau metabolism, and that autophagy dysfunction exacerbates amyloidosis and tau pathology. Therefore, targeting autophagy may be an effective approach for the treatment of AD. Animal models are considered useful tools for investigating the pathogenic mechanisms and therapeutic strategies of diseases. This review aims to summarize the pathological alterations in autophagy in representative AD animal models and to present recent studies on newly discovered autophagy-stimulating interventions in animal AD models. Finally, the opportunities, difficulties, and future directions of autophagy targeting in AD therapy are discussed.

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5xFAD mice do not have myenteric amyloidosis, dysregulation of neuromuscular transmission or gastrointestinal dysmotility

Cited by 4 publications

References 36 publications

Single-cell transcriptomics reveals colonic immune perturbations during amyloid-β driven Alzheimer’s disease in mice

Single-cell transcriptomics reveals colonic immune perturbations during amyloid-β driven Alzheimer’s disease in mice

The Aging Enteric Nervous System

Targeting autophagy in Alzheimer’s disease: Animal models and mechanisms

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