Therapeutic effects of anti-amyloid β antibody after intravenous injection and efficient nose-to-brain delivery in Alzheimer’s disease mouse model

Background: Alzheimer’s disease (AD) is the most general, chronic, and progressive neurodegenerative senile disorder characterized clinically by progressive cognitive deterioration and memory impairment. Neoline is effective against neuropathic pain models, but the effects of neoline against AD-like phenotypes have not been investigated. Objective: We offer the investigation of the effects of neoline in AD. Methods: In this study, a Tg-APPswe/PS1dE9 AD mouse model was treated orally with neoline at a concentration of 0.5 mg/kg or 0.1 mg/kg starting at 7.5 months and administered for three months, and its anti-AD effects were evaluated. Results: Neoline improved memory and cognition impairments and reduced the number of amyloid-beta plaque and the amount of amyloid-β in the brain of AD mice. Furthermore, neoline reduced the anxiety behavior in the AD mouse model. The chronic administration of neoline also induced AMPK phosphorylation and decreased tau, amyloid-β, and BACE1 expression in the hippocampus. These findings indicate that chronic administration of neoline has therapeutic effects via AMPK activation, and BACE1 downregulation resulted in a decrease in the amyloid-β levels in the brain of Tg-APPswe/PS1dE9 AD mice. Conclusion: Our results suggest that neoline is a therapeutic agent for the cure of neurodegenerative diseases like AD.

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Anti-Amyloid-β Single-Chain Antibody Brain Delivery Via AAV Reduces Amyloid Load But May Increase Cerebral Hemorrhages in an Alzheimer's Disease Mouse Model

Journal of Alzheimer s Disease ◽

10.3233/jad-2011-110230 ◽

2011 ◽

Vol 27 (1) ◽

pp. 23-38 ◽

Cited By ~ 22

Author(s):

Jinghong Kou ◽

HongDuck Kim ◽

Abhinandan Pattanayak ◽

Min Song ◽

Jeong-Eun Lim ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Amyloid Β ◽

Brain Delivery ◽

Single Chain ◽

Single Chain Antibody ◽

Amyloid Load

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The Therapeutic Effects of the Herbal Medicine, Juzen-taiho-to, on Amyloid-β Burden in a Mouse Model of Alzheimer's Disease

Journal of Alzheimer s Disease ◽

10.3233/jad-2010-1381 ◽

2010 ◽

Vol 20 (2) ◽

pp. 427-439 ◽

Cited By ~ 15

Author(s):

Hideo Hara ◽

Seiko Kataoka ◽

Mayumi Anan ◽

Akihiro Ueda ◽

Tatsuro Mutoh ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Herbal Medicine ◽

Mouse Model ◽

Amyloid Β ◽

Therapeutic Effects ◽

Model Of Alzheimer’S Disease

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High‐Fat Diet Modulates Hepatic Amyloid β and Cerebrosterol Metabolism in the Triple Transgenic Mouse Model of Alzheimer’s Disease

Hepatology Communications ◽

10.1002/hep4.1609 ◽

2020 ◽

Author(s):

Cristina R. Bosoi ◽

Milène Vandal ◽

Marine Tournissac ◽

Manon Leclerc ◽

Hortense Fanet ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Transgenic Mouse ◽

High Fat Diet ◽

Amyloid Β ◽

Transgenic Mouse Model ◽

High Fat ◽

Model Of Alzheimer’S Disease ◽

Triple Transgenic Mouse

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24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

Marine Drugs ◽

10.3390/md19040190 ◽

2021 ◽

Vol 19 (4) ◽

pp. 190

Author(s):

Nikita Martens ◽

Melissa Schepers ◽

Na Zhan ◽

Frank Leijten ◽

Gardi Voortman ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Cognitive Decline ◽

Inflammatory Marker ◽

Amyloid Β ◽

Liver Fat ◽

Gas Chromatography Mass Spectrometry ◽

Memory Decline ◽

Plaque Load

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

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Impaired spike-gamma coupling of area CA3 fast-spiking interneurons as the earliest functional impairment in the AppNL-G-F mouse model of Alzheimer’s disease

Molecular Psychiatry ◽

10.1038/s41380-021-01257-0 ◽

2021 ◽

Author(s):

Luis Enrique Arroyo-García ◽

Arturo G. Isla ◽

Yuniesky Andrade-Talavera ◽

Hugo Balleza-Tapia ◽

Raúl Loera-Valencia ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mouse Model ◽

Functional Impairment ◽

Amyloid Β ◽

Gamma Oscillations ◽

Gamma Oscillation ◽

Gamma Rhythm ◽

Fast Spiking

AbstractIn Alzheimer’s disease (AD) the accumulation of amyloid-β (Aβ) correlates with degradation of cognition-relevant gamma oscillations. The gamma rhythm relies on proper neuronal spike-gamma coupling, specifically of fast-spiking interneurons (FSN). Here we tested the hypothesis that decrease in gamma power and FSN synchrony precede amyloid plaque deposition and cognitive impairment in AppNL-G-F knock-in mice (AppNL-G-F). The aim of the study was to evaluate the amyloidogenic pathology progression in the novel AppNL-G-F mouse model using in vitro electrophysiological network analysis. Using patch clamp of FSNs and pyramidal cells (PCs) with simultaneous gamma oscillation recordings, we compared the activity of the hippocampal network of wild-type mice (WT) and the AppNL-G-F mice at four disease stages (1, 2, 4, and 6 months of age). We found a severe degradation of gamma oscillation power that is independent of, and precedes Aβ plaque formation, and the cognitive impairment reported previously in this animal model. The degradation correlates with increased Aβ1-42 concentration in the brain. Analysis on the cellular level showed an impaired spike-gamma coupling of FSN from 2 months of age that correlates with the degradation of gamma oscillations. From 6 months of age PC firing becomes desynchronized also, correlating with reports in the literature of robust Aβ plaque pathology and cognitive impairment in the AppNL-G-F mice. This study provides evidence that impaired FSN spike-gamma coupling is one of the earliest functional impairment caused by the amyloidogenic pathology progression likely is the main cause for the degradation of gamma oscillations and consequent cognitive impairment. Our data suggests that therapeutic approaches should be aimed at restoring normal FSN spike-gamma coupling and not just removal of Aβ.

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