scholarly journals Anti-Inflammatory Gene Therapy Improves Spatial Memory Performance in a Mouse Model of Alzheimer’s Disease

2021 ◽  
pp. 1-8
Author(s):  
Tai June Yoo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Therapy ◽  
Mouse Model ◽  
Spatial Memory ◽  
Memory Performance ◽  
Critical Role ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Anti Inflammatory

The immune system plays a critical role in neurodegenerative processes involved in Alzheimer’s disease (AD). In this study, a gene-based immunotherapeutic method examined the effects of anti-inflammatory cellular immune response elements (CIREs) in the amyloid-β protein precursor (AβPP) mouse model. Bi-monthly intramuscular administration, beginning at either 4 or 6 months, and examined at 7.5 through 16 months, with plasmids encoding Interleukin (IL)-10, IL-4, TGF-β polynucleotides, or a combination thereof, into AβPP mice improved spatial memory performance. This work demonstrates an efficient gene therapy strategy to downregulate neuroinflammation, and possibly prevent or delay cognitive decline in AD.

scholarly journals Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer’s disease mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Fujita ◽  
Kuniyuki Kano ◽  
Shigenobu Kishino ◽  
Toshihiro Nagao ◽  
Xuefeng Shen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Linoleic Acid ◽  
Mouse Model ◽  
Conjugated Linoleic Acid ◽  
Inflammatory Cytokines ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Anti Inflammatory ◽  
The Brain

AbstractConjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer’s disease (AD) remain to be elucidated. In this study, we investigated the effect of dietary intake of c-9, t-11-CLA on the pathogenesis of an AD mouse model. We found that c-9, t-11-CLA diet-fed AD model mice significantly exhibited (1) a decrease in amyloid-β protein (Aβ) levels in the hippocampus, (2) an increase in the number of microglia, and (3) an increase in the number of astrocytes expressing the anti-inflammatory cytokines, interleukin-10 and 19 (IL-10, IL-19), with no change in the total number of astrocytes. In addition, liquid chromatography–tandem mass spectrometry (LC–MS/MS) and gas chromatographic analysis revealed that the levels of lysophosphatidylcholine (LPC) containing c-9, t-11-CLA (CLA-LPC) and free c-9, t-11-CLA were significantly increased in the brain of c-9, t-11-CLA diet-fed mice. Thus, dietary c-9, t-11-CLA entered the brain and appeared to exhibit beneficial effects on AD, including a decrease in Aβ levels and suppression of inflammation.

scholarly journals CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease

2008 ◽  
Vol 205 (7) ◽  
pp. 1593-1599 ◽  
Author(s):  
Michael Bacher ◽  
Richard Dodel ◽  
Bayan Aljabari ◽  
Kathy Keyvani ◽  
Philippe Marambaud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory Performance ◽  
Amyloid Β ◽  
Amyloid Plaque ◽  
Amyloid Β Protein ◽  
Aβ Oligomers ◽  
App Processing ◽  
Model Of Alzheimer’S Disease

Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid β protein (Aβ) peptide “oligomers” and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent guanylhydrazone with established antiinflammatory properties, interferes with Aβ assembly and protects neuronal cells from the toxic effect of soluble Aβ oligomers. Administration of CNI-1493 to TgCRND8 mice overexpressing human amyloid precursor protein (APP) for a treatment period of 8 wk significantly reduced Aβ deposition. CNI-1493 treatment resulted in 70% reduction of amyloid plaque area in the cortex and 87% reduction in the hippocampus of these animals. Administration of CNI-1493 significantly improved memory performance in a cognition task compared with vehicle-treated mice. In vitro analysis of CNI-1493 on APP processing in an APP-overexpressing cell line revealed a significant dose-dependent decrease of total Aβ accumulation. This study indicates that the antiinflammatory agent CNI-1493 can ameliorate the pathophysiology and cognitive defects in a murine model of AD.

Passage of amyloid β protein antibody across the blood–brain barrier in a mouse model of Alzheimer’s disease

Peptides ◽  
2002 ◽  
Vol 23 (12) ◽  
pp. 2223-2226 ◽  
Author(s):  
William A. Banks ◽  
Brie Terrell ◽  
Susan A. Farr ◽  
Sandra M. Robinson ◽  
Naoko Nonaka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Amyloid Β Protein ◽  
Blood Brain ◽  
Model Of Alzheimer’S Disease ◽  
Β Protein

scholarly journals Spatial memory deficiency early in 6xTg Alzheimer’s disease mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinwoo Kang ◽  
Jinho Kim ◽  
Keun-A Chang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Spatial Memory ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Cognitive Changes ◽  
Synaptic Loss ◽  
5Xfad Mice ◽  
Ad Mouse Model

AbstractAlzheimer’s disease (AD) is mainly characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFTs). While the recent 5xFAD AD mouse model exhibits many AD-related phenotypes and a relatively early and aggressive amyloid β production, it does not show NFTs. Here, we developed and evaluated a novel AD mouse model (6xTg-AD, 6xTg) by crossbreeding 5xFAD mice with mice expressing mutant (P301L) tau protein (MAPT). Through behavioral and histopathological tests, we analyzed cognitive changes and neuropathology in 6xTg mice compared to their respective parental strains according to age. Spatial memory deficits occurred in 6xTg mice at 2 months of age, earlier than they occurred in 5xFAD mice. Histopathological data revealed aggressive Aβ42 and p-tau accumulation in 6xTg mice. Microglial activation occurred in the cortex and hippocampus of 6xTg mice beginning at 2 months. In 6xTg model mice, the synaptic loss was observed in the cortex from 4 months of age and in the hippocampus from 6 months of age, and neuronal loss appeared in the cortex from 4 months of age and in the hippocampus 6 months of age, earlier than it is observed in the 5xFAD and JNPL3 models. These results showed that each pathological symptom appeared much faster than in their parental animal models. In conclusion, these novel 6xTg-AD mice might be an advanced animal model for studying AD, representing a promising approach to developing effective therapy.

scholarly journals Protection against Amyloid-β Oligomer Neurotoxicity by Small Molecules with Antioxidative Properties: Potential for the Prevention of Alzheimer’s Disease Dementia

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 132
Author(s):  
Wataru Araki ◽  
Fuyuki Kametani
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecules ◽  
Critical Role ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Aβ Oligomers ◽  
Antioxidative Properties ◽  
Drug Candidates ◽  
Β Protein

Soluble oligomeric assemblies of amyloid β-protein (Aβ), called Aβ oligomers (AβOs), have been recognized as primary pathogenetic factors in the molecular pathology of Alzheimer’s disease (AD). AβOs exert neurotoxicity and synaptotoxicity and play a critical role in the pathological progression of AD by aggravating oxidative and synaptic disturbances and tau abnormalities. As such, they are important therapeutic targets. From a therapeutic standpoint, it is not only important to clear AβOs or prevent their formation, it is also beneficial to reduce their neurotoxicity. In this regard, recent studies have reported that small molecules, most with antioxidative properties, show promise as therapeutic agents for reducing the neurotoxicity of AβOs. In this mini-review, we briefly review the significance of AβOs and oxidative stress in AD and summarize studies on small molecules with AβO-neurotoxicity-reducing effects. We also discuss mechanisms underlying the effects of these compounds against AβO neurotoxicity as well as their potential as drug candidates for the prevention and treatment of AD.

scholarly journals Distinguishing Amyloid β-Protein in a Mouse Model of Alzheimer’s Disease by Label-Free Vibrational Imaging

Biosensors ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 365
Author(s):  
Shaowei Li ◽  
Ziyi Luo ◽  
Renlong Zhang ◽  
Hao Xu ◽  
Ting Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Β ◽  
Basic Research ◽  
Amyloid Β Protein ◽  
Label Free ◽  
Model Of Alzheimer’S Disease ◽  
Β Protein ◽  
Anti Stokes

Due to the increase in the average age of humans, Alzheimer’s disease (AD) has become one of the disorders with the highest incidence worldwide. Abnormal amyloid β protein (Aβ) accumulation is believed to be the most common cause of AD. Therefore, distinguishing the lesion areas can provide clues for AD diagnosis. Here, we present an optical spectroscopy and imaging approach based on coherent anti-Stokes Raman scattering (CARS). Label-free vibrational imaging of Aβ in a mouse model of AD was performed to distinguish the lesion areas by studying the spectra of regions with and without Aβ plaques. Raman spectra in Aβ and non-Aβ regions exhibited a specific difference in the intensity ratio of the wave peaks detected at 2850 and 2930 cm–1. In the non-Aβ region, the ratio of the peak intensity at 2850 cm–1 to that at 2930 cm–1 was approximately 1, whereas that in the Aβ region was 0.8. This label-free vibrational imaging may provide a new method for the clinical diagnosis and basic research of AD.

scholarly journals Acat1 Knockdown Gene Therapy Decreases Amyloid-β in a Mouse Model of Alzheimer's Disease

2013 ◽  
Vol 21 (8) ◽  
pp. 1497-1506 ◽  
Author(s):  
Stephanie R Murphy ◽  
Catherine CY Chang ◽  
Godwin Dogbevia ◽  
Elena Y Bryleva ◽  
Zachary Bowen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gene Therapy ◽  
Mouse Model ◽  
Amyloid Β ◽  
Model Of Alzheimer’S Disease
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