scholarly journals Bioluminescent imaging in an Alzheimer's disease (AD) mouse model tracking β-amyloid (Aβ) deposits

2011 ◽  
Vol 4 (7) ◽  
pp. 202-202
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Bioluminescent Imaging ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Ad Mouse Model

scholarly journals Microglia modulation with 1070-nm light attenuates Aβ burden and cognitive impairment in Alzheimer’s disease mouse model

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Lechan Tao ◽  
Qi Liu ◽  
Fuli Zhang ◽  
Yuting Fu ◽  
Xi Zhu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Near Infrared ◽  
Biological Responses ◽  
Near Infrared Spectra ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Aβ Clearance ◽  
Ad Mouse Model

AbstractPhotobiomodulation, by utilizing low-power light in the visible and near-infrared spectra to trigger biological responses in cells and tissues, has been considered as a possible therapeutic strategy for Alzheimer’s disease (AD), while its specific mechanisms have remained elusive. Here, we demonstrate that cognitive and memory impairment in an AD mouse model can be ameliorated by 1070-nm light via reducing cerebral β-amyloid (Aβ) burden, the hallmark of AD. The glial cells, including microglia and astrocytes, play important roles in Aβ clearance. Our results show that 1070-nm light pulsed at 10 Hz triggers microglia rather than astrocyte responses in AD mice. The 1070-nm light-induced microglia responses with alteration in morphology and increased colocalization with Aβ are sufficient to reduce Aβ load in AD mice. Moreover, 1070-nm light pulsed at 10 Hz can reduce perivascular microglia and promote angiogenesis to further enhance Aβ clearance. Our study confirms the important roles of microglia and cerebral vessels in the use of 1070-nm light for the treatment of AD mice and provides a framework for developing a novel therapeutic approach for AD.

scholarly journals Methionine sulfoxide reductase A affects β-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease

2016 ◽  
Vol 310 (6) ◽  
pp. E388-E393 ◽  
Author(s):  
Jackob Moskovitz ◽  
Fang Du ◽  
Connor F. Bowman ◽  
Shirley S. Yan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase ◽  
Methionine Sulfoxide Reductase A ◽  
Model Of Alzheimer’S Disease ◽  
Amyloid Aβ ◽  
Β Amyloid

Accumulation of oxidized proteins, and especially β-amyloid (Aβ), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Aβ through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Aβ in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Aβ. Indeed, the novel MsrA-deficient APP mice ( APP+/ MsrAKO) exhibited higher levels of soluble Aβ in brain compared with APP+ mice. Furthermore, mitochondrial respiration and the activity of cytochrome c oxidase were compromised in the APP+/ MsrAKO compared with control mice. These results suggest that lower MsrA activity modifies Aβ solubility properties and causes mitochondrial dysfunction, and augmenting its activity may be beneficial in delaying AD progression.

scholarly journals O-GlcNAcylation ameliorates the pathological manifestations of Alzheimer’s disease by inhibiting necroptosis

2021 ◽  
Vol 7 (3) ◽  
pp. eabd3207
Author(s):  
Jinsu Park ◽  
Hee-Jin Ha ◽  
Eun Seon Chung ◽  
Seung Hyun Baek ◽  
Yoonsuk Cho ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Loss ◽  
Protective Role ◽  
Tau Pathology ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
5Xfad Mice ◽  
Ad Mouse Model ◽  
M2 Phenotype

O-GlcNAcylation (O-linked β-N-acetylglucosaminylation) is notably decreased in Alzheimer’s disease (AD) brain. Necroptosis is activated in AD brain and is positively correlated with neuroinflammation and tau pathology. However, the links among altered O-GlcNAcylation, β-amyloid (Aβ) accumulation, and necroptosis are unclear. Here, we found that O-GlcNAcylation plays a protective role in AD by inhibiting necroptosis. Necroptosis was increased in AD patients and AD mouse model compared with controls; however, decreased necroptosis due to O-GlcNAcylation of RIPK3 (receptor-interacting serine/threonine protein kinase 3) was observed in 5xFAD mice with insufficient O-linked β-N-acetylglucosaminase. O-GlcNAcylation of RIPK3 suppresses phosphorylation of RIPK3 and its interaction with RIPK1. Moreover, increased O-GlcNAcylation ameliorated AD pathology, including Aβ burden, neuronal loss, neuroinflammation, and damaged mitochondria and recovered the M2 phenotype and phagocytic activity of microglia. Thus, our data establish the influence of O-GlcNAcylation on Aβ accumulation and neurodegeneration, suggesting O-GlcNAcylation–based treatments as potential interventions for AD.

MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Dan Wang ◽  
Zhifu Fei ◽  
Song Luo ◽  
Hai Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Western Blot ◽  
Mrna Expression ◽  
Cognitive Deficits ◽  
Protein Levels ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

scholarly journals P3-270: CHF5074 reduces brain β-amyloid burden and hyperphosphorylated tau in a mouse model of Alzheimer's disease

2009 ◽  
Vol 5 (4S_Part_14) ◽  
pp. P422-P422
Author(s):  
M. Pizzi ◽  
A. Lanzillotta ◽  
B.P. Imbimbo ◽  
B. Hutter-Paier ◽  
G. Villetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Hyperphosphorylated Tau ◽  
Amyloid Burden ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid

scholarly journals Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease

2005 ◽  
Vol 171 (1) ◽  
pp. 87-98 ◽  
Author(s):  
W. Haung Yu ◽  
Ana Maria Cuervo ◽  
Asok Kumar ◽  
Corrinne M. Peterhoff ◽  
Stephen D. Schmidt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Survival ◽  
Mammalian Target Of Rapamycin ◽  
Amyloid Peptide ◽  
Survival Pathways ◽  
Secretase Activity ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before β-amyloid (Aβ) deposits extracellularly in the presenilin (PS) 1/Aβ precursor protein (APP) mouse model of β-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Aβ. Purified AVs contain APP and β-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent γ-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Aβ production. Our results, therefore, link β-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.

Distance-based β-amyloid protein detection on PADs for scanning and subsequent follow up of Alzheimer’s disease in human urine sample

The Analyst ◽  
2022 ◽  
Author(s):  
Kawin Khachornsakkul ◽  
Anongnat Tiangtrong ◽  
Araya Suwannasom ◽  
Wuttichai Sangkharoek ◽  
Opor Jamjumrus ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Urine ◽  
Protein Detection ◽  
Protein Quantification ◽  
Amyloid Protein ◽  
Human Urine Sample ◽  
Amyloid Aβ ◽  
Β Amyloid

We report on the first development of a simple distance-based β-amyloid (Aβ) protein quantification using paper-based devices (dPADs) to screen for Alzheimer’s disease (AD) and to subsequently follow up on...

Non-uinform gut microbiota alteration patterns associated with therapeutic outcomes in an Alzheimer's disease animal model

2019 ◽  
Author(s):  
Min Wang ◽  
William Kwame Amakye ◽  
Jianing Cao ◽  
Congcong Gong ◽  
Xiaoyu Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Outcomes ◽  
Targeted Treatments ◽  
Amyloid Aβ

Abstract Background: Dysbiosis of gut microbiota is associated with the progression of beta-amyloid (Aβ) pathology in Alzheimer’s disease (AD). We aimed to identify uniform Aβ-responsible gut microbiota status as possible guideline for gut microbiota manipulation and the prediction of outcomes of microbiota targeted treatments. Six months old APP/PS1 mice from the same genetic background, housing and feeding conditions were then daily gavage with Metformin, peptides WN5 or PW5 to manipulate the gut microbiota for 12 weeks. Aβ pathology and gut microbiota were then explored and compared. Results: Fecal microbiota transplantation (FMT) from a 16 month old APP/PS1 mouse reconstituted the gut microbiota towards the donor and increased Aβ pathology in APP/PS1 mouse model. Metformin, peptides WN5 and PW5 all attenuated Aβ-plaque formation in APP/PS1 mouse model but each was associated with distinct gut microbiota status. No uniform gut microbiota pattern associated with Aβ pathology was found among different gut microbiota-targeted treatments. Conclusion: We found no uniform gut microbiota status associated with Aβ pathology suggesting gut microbiota status is not a suitable biomarker for AD diagnosis and treatment predictions. Alteration of gut microbiota in itself may not be sufficiently directly related to functional outcomes and might only be a shadow of deeper molecular mechanisms not fully understood. The findings here strongly suggested that the significance of gut microbiota alteration in disease pathology and treatment may have so far been over claimed and that interpretation of gut microbiota data should be done with utmost caution.

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