scholarly journals microRNA-132/212 deficiency enhances Aβ production and senile plaque deposition in Alzheimer’s disease triple transgenic mice

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Julia Hernandez-Rapp ◽  
Sara Rainone ◽  
Claudia Goupil ◽  
Véronique Dorval ◽  
Pascal Y. Smith ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Senile Plaque ◽  
Plaque Deposition ◽  
Aβ Production

scholarly journals Caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1 in Alzheimer’s disease

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Xunhu Gu ◽  
Hanjun Wu ◽  
Yuqin Xie ◽  
Lijun Xu ◽  
Xu Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Membrane Transport ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Senile Plaque ◽  
Spatial Learning And Memory ◽  
Memory Ability ◽  
Caspase 1 ◽  
Plaque Deposition

Abstract Background Alzheimer's disease is a neurodegenerative disease. Previous study has reported that caspase-1/IL-1β is closely associated with Alzheimer's disease. However, the biological role of caspase-1/IL-1β in Alzheimer's disease has not been fully elucidated. This study aimed to explore the mechanism of action of caspase-1/IL-1β in Alzheimer's disease. Methods Mouse hippocampal neurones were treated with Aβ1-42 to induce Alzheimer's disease cell model. APP/PS1 mice and Aβ1-42-induced hippocampal neurones were treated with AC-YVAD-CMK (caspase-1 inhibitor). Spatial learning and memory ability of mice were detected by morris water maze. Flow cytometry, TUNEL staining, Thioflavin S staining and immunohistochemistry were performed to examine apoptosis and senile plaque deposition. Enzyme linked immunosorbent assay and western blot were performed to assess the levels of protein or cytokines. Co-Immunoprecipitation was performed to verify the interaction between Stargazin and GluA1. Results AC-YVAD-CMK treatment improved spatial learning and memory ability and reduced senile plaque deposition of APP/PS1 mice. Moreover, AC-YVAD-CMK promoted membrane transport of GluA1 in APP/PS1 mice. In vitro, Aβ1-42-induced hippocampal neurones exhibited an increase in apoptosis and a decrease in the membrane transport of GluA1, which was abolished by AC-YVAD-CMK treatment. In addition, Stargazin interacted with GluA1, which was repressed by caspase-1. Caspase-1/IL-1β inhibited membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1. Conclusions Our data demonstrate that caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin in Alzheimer's disease. Thus, caspase-1/IL-1β may be a target for Alzheimer's disease treatment.

scholarly journals The Role of APP O-Glycosylation in Alzheimer’s Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1569
Author(s):  
Keiko Akasaka-Manya ◽  
Hiroshi Manya
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaque ◽  
Amyloid Β ◽  
Pathological Feature ◽  
People With Dementia ◽  
New Findings ◽  
Neurodegenerative Dementia ◽  
Aβ Production

The number of people with dementia is increasing rapidly due to the increase in the aging population. Alzheimer’s disease (AD) is a type of neurodegenerative dementia caused by the accumulation of abnormal proteins. Genetic mutations, smoking, and several other factors have been reported as causes of AD, but alterations in glycans have recently been demonstrated to play a role in AD. Amyloid-β (Aβ), a cleaved fragment of APP, is the source of senile plaque, a pathological feature of AD. APP has been reported to undergo N- and O-glycosylation, and several Polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) have been shown to have catalytic activity for the transfer of GalNAc to APP. Since O-glycosylation in the proximity of a cleavage site in many proteins has been reported to be involved in protein processing, O-glycans may affect the cleavage of APP during the Aβ production process. In this report, we describe new findings on the O-glycosylation of APP and Aβ production.

scholarly journals Delta-secretase triggers Alzheimer’s disease pathologies in wild-type hAPP/hMAPT double transgenic mice

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Zhourui Wu ◽  
Xia Liu ◽  
Liming Cheng ◽  
Keqiang Ye
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Senile Plaques ◽  
Wild Type ◽  
Double Transgenic Mouse ◽  
Double Transgenic Mice ◽  
One Year ◽  
Aβ Production ◽  
Human Wild Type

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disease with multifactorial pathologies including Aβ containing senile plaques and neurofibrillary tangles (NFT) consisted of aggregated Tau. Most of the AD patients are sporadic and the familial mutation hereditary patients are composed only 1% of all cases. However, the current AD mouse models employ mutated APP, PS1, or even Tau mutant, in order to display a portion of AD pathologies. Delta-secretase (legumain, or asparaginyl endopeptidase, AEP) simultaneously cleaves both APP and Tau and augments Aβ production and Tau hyperphosphorylation and aggregation, contributing to AD pathogenesis. Here we show that δ-secretase is sufficient to promote prominent AD pathologies in wild-type hAPP/hMAPT double transgenic mice. We crossed hAPP l5 mice and hMAPT mice to generate double transgenic mouse model carrying both human wild-type APP and Tau. Compared to the single transgenic parents, these double transgenic mice demonstrated AD-related pathologies in one-year-old hAPP/hMAPT mice. Notably, overexpression of δ-secretase in hAPP/hMAPT double-transgenic mice evidently accelerated enormous senile plaques and NFT, associated with prominent synaptic defects and cognitive deficits. Hence, δ-secretase facilitates AD pathogenesis independent of any patient-derived mutation.

P2-010: Improved quantitative accuracy for early diagnosis of plaque deposition in Alzheimer's disease in transgenic mice

2011 ◽  
Vol 7 ◽  
pp. S308-S309
Author(s):  
Nikolai Slavine ◽  
Padmakar Kulkarni ◽  
Roderick McColl ◽  
Anjali Gupta ◽  
Veera Aurora ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Transgenic Mice ◽  
Plaque Deposition ◽  
Quantitative Accuracy

IC-P-005: Improved quantitative accuracy for early diagnosis of plaque deposition in Alzheimer's disease in transgenic mice

2011 ◽  
Vol 7 ◽  
pp. S9-S10
Author(s):  
Nikolai Slavine ◽  
Padmakar Kulkarni ◽  
Roderick McColl ◽  
Anjali Gupta ◽  
Veera Aurora ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Transgenic Mice ◽  
Plaque Deposition ◽  
Quantitative Accuracy

scholarly journals Vaccine Development to Treat Alzheimer’s Disease Neuropathology in APP/PS1 Transgenic Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Iván Carrera ◽  
Ignacio Etcheverría ◽  
Lucía Fernández-Novoa ◽  
Valter Lombardi ◽  
Ramón Cacabelos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
T Cell Activation ◽  
Cell Activation ◽  
Vaccine Development ◽  
Senile Plaque ◽  
Neurofibrillary Tangle ◽  
Plaque Burden ◽  
Activation Markers

A novel vaccine addressing the major hallmarks of Alzheimer’s disease (AD), senile plaque-like deposits of amyloid beta-protein (Aβ), neurofibrillary tangle-like structures, and glial proinflammatory cytokines, has been developed. The present vaccine takes a new approach to circumvent failures of previous ones tested in mice and humans, including the Elan-Wyeth vaccine (AN1792), which caused massive T-cell activation, resulting in a meningoencephalitis-like reaction. The EB101 vaccine consists ofAβ1-42delivered in a novel immunogen-adjuvant composed of liposomes-containing sphingosine-1-phosphate (S1P). EB101 was administered to APPswe/PS1dE9 transgenic mice before and after AD-like pathological symptoms were detectable. Treatment with EB101 results in a marked reduction of Aβplaque burden, decrease of neurofibrillary tangle-like structure density, and attenuation of astrocytosis. In this transgenic mouse model, EB101 reduces the basal immunological interaction between the T cells and immune activation markers in the affected hippocampal/cortical areas, consistent with decreased amyloidosis-induced inflammation. Therefore, immunization with EB101 prevents and reverses AD-like neuropathology in a significant manner by halting disease progression without developing behavioral spatial deficits in transgenic mice.

scholarly journals BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer’s disease

2018 ◽  
Vol 115 (15) ◽  
pp. 3954-3959 ◽  
Author(s):  
Jian Bao ◽  
Min Qin ◽  
Yacoubou Abdoul Razak Mahaman ◽  
Bin Zhang ◽  
Fang Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Protease Activity ◽  
Senile Plaque ◽  
Critical Role ◽  
Wild Type ◽  
Rate Limiting ◽  
Aβ Production ◽  
Ad Mouse Model

Amyloid beta (Aβ) is a major pathological marker in Alzheimer’s disease (AD), which is principally regulated by the rate-limiting β-secretase (i.e., BACE1) cleavage of amyloid precursor protein (APP). However, how BACE1 activity is posttranslationally regulated remains incompletely understood. Here, we show that BACE1 is predominantly SUMOylated at K501 residue, which escalates its protease activity and stability and subsequently increases Aβ production, leading to cognitive defect seen in the AD mouse model. Compared with a non-SUMOylated K501R mutant, injection of wild-type BACE1 significantly increases Aβ production and triggers cognitive dysfunction. Furthermore, overexpression of wild-type BACE1, but not non-SUMOylated K501R mutant, facilitates senile plaque formation and aggravates the cognitive deficit seen in the APP/PS1 AD mouse model. Together, our data strongly suggest that K501 SUMOylation on BACE1 plays a critical role in mediating its stability and enzymatic activity.

scholarly journals Long-term dynamics of aberrant neuronal activity in awake Alzheimer’s disease transgenic mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
V. Korzhova ◽  
P. Marinković ◽  
J. Rudan Njavro ◽  
P. M. Goltstein ◽  
F. Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Neuronal Activity ◽  
Amyloid Plaque ◽  
Observation Time ◽  
Cerebral Amyloidosis ◽  
Plaque Deposition ◽  
Highly Active

AbstractAlzheimer’s disease (AD) is associated with aberrant neuronal activity, which is believed to critically determine disease symptoms. How these activity alterations emerge, how stable they are over time, and whether cellular activity dynamics are affected by the amyloid plaque pathology remains incompletely understood. We here repeatedly recorded the activity from identified neurons in cortex of awake APPPS1 transgenic mice over four weeks during the early phase of plaque deposition using in vivo two-photon calcium imaging. We found that aberrant activity during this stage largely persisted over the observation time. Novel highly active neurons slowly emerged from former intermediately active neurons. Furthermore, activity fluctuations were independent of plaque proximity, but aberrant activity was more likely to persist close to plaques. These results support the notion that neuronal network pathology observed in models of cerebral amyloidosis is the consequence of persistent single cell aberrant neuronal activity, a finding of potential diagnostic and therapeutic relevance for AD.

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