Lixisenatide reduces amyloid plaques, neurofibrillary tangles and neuroinflammation in an APP/PS1/tau mouse model of Alzheimer's disease

Cai, Hong-Yan; Yang, Junting; Wang, Zhaojun; Zhang, Jun; Yang, Weiren; Wu, Mei‐Na; Qi, Jin-Shun

doi:10.1016/j.bbrc.2017.11.114

Cited by 79 publications

(53 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is reported that T2DM can promote higher level of β-amyloid protein (plaques) and hyperphosphorylation of Tau protein in cerebrospinal fluid, which resembles the pathological process of AD (Moran et al, 2015). Antidiabetic treatment can ameliorate the cognitive impairment of AD patients and improve their learning and executive processing function (Cai et al, 2018;Infante-Garcia et al, 2018). All those evidence indicate that hyperglycemia affects AD in a variety of forms.…”

Section: Introductionmentioning

confidence: 96%

Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer’s Disease patients analyzed by MRI: a retrospective study

Wang

Wong

Shi

et al. 2020

PeerJ

View full text Add to dashboard Cite

Objectives Alzheimer’s disease (AD), impaired fasting glucose (IFG), and Type 2 diabetes mellitus (T2DM) were reported associated with smaller brain volumes. Nevertheless, the association of hyperglycemia with brain volume changes in AD patients remains unclear. To investigate this issue, structural magnetic resonance imaging was used to compare brain volumes among AD patients with different fasting glucose levels. Methods Eighty-five AD patients were divided into three groups based on their fasting glucose level as suggested by the American Diabetes Association: normal fasting glucose group (AD_NFG, n = 45), AD_IFG group (n = 15), and AD_T2DM group (n = 25). Sagittal 3D T1-weighted images were obtained to calculate the brain volume. Brain parenchyma and 33 brain structures were automatically segmented. Each regional volume was analyzed among groups. For regions with statistical significance, partial correlation analysis was used to evaluate their relationships with fasting glucose level, corrected for Mini-Mental State Examination score, age, education level, cholesterol, triglyceride, and blood pressure. Results Compared with the AD_IFG and AD_NFG groups, the volume of pons in AD_T2DM group was significantly smaller. Fasting glucose was negatively correlated with pontine volume. Conclusions T2DM may exacerbate pontine atrophy in AD patients, and fasting glucose level is associated with pontine volume.

show abstract

Section: Introductionmentioning

confidence: 96%

Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer’s Disease patients analyzed by MRI: a retrospective study

Wang

Wong

Shi

et al. 2020

PeerJ

View full text Add to dashboard Cite

show abstract

“…Liraglutide, an acetylated analogue of GLP-1, has been shown to reverse memory impairments and reduced synaptic plasticity (LTP) in the hippocampus of transgenic mouse models of AD (McClean & Hoelscher, 2014a;McClean et al, 2011). Lixisenatide is a new GLP-1 receptor agonist that shows neuroprotective effects in animal models of AD (Cai et al, 2017(Cai et al, , 2018McClean & Hoelscher, 2014a, 2014b. Glucose-dependent insulinotropic polypeptide (GIP) is a sister hormone of GLP-1 with similar properties as GLP-1 (Lund, Vilsboll, Bagger, Holst, & Knop, 2011).…”

Section: Introductionmentioning

confidence: 99%

The novel GLP‐1/GIP analogue DA5‐CH reduces tau phosphorylation and normalizes theta rhythm in the icv. STZ rat model of AD

Cheng

Liu

et al. 2020

Brain and Behavior

View full text Add to dashboard Cite

Introduction Alzheimer's disease (AD) is the most common progressive neurodegenerative disease for which there is no cure. Recent studies have shown a close link between type 2 diabetes and AD, which suggested that drugs for type 2 diabetes may be effective for AD. GLP‐1 and GIP are incretin hormones that can ameliorate diabetes. Methods In the present study, we tested the novel dual GLP‐1/GIP receptor agonist DA5‐CH in the icv. streptozotocin (STZ)‐induced insulin desensitization model of AD in rats to explore the protective effects of DA5‐CH. Results The results show that DA5‐CH could reverse the STZ‐induced working memory impairments in a Y‐maze tests, and spatial memory impairments in the water maze task, and decrease the levels of phosphorylated tauS396 protein in the hippocampus. In EEG recordings, STZ treatment diminished the power of the theta band frequency. DA5‐CH was able to increase the energy of theta band activity in the hippocampal CA1 region. The drug also increased the expression of synapse‐related proteins in the hippocampus. After DA5‐CH treatment, mitochondrial stress was alleviated as shown by the improved ratio of Bax/Bcl‐2 in the hippocampus. Growth factor signaling was also normalized as shown by the increased level of the transcription factor P‐CREBS133. In addition, we were able to show that DA5‐CH can cross the blood–brain barrier at an increased rate compared with other dual GLP‐1/GIP or single GLP‐1 receptor agonists. Conclusion Therefore, our results demonstrate that DA5‐CH has neuroprotective effects in the STZ‐induced animal model and that DA5‐CH has potential to treat neurodegenerative disorders such as AD.

show abstract

“…Henceforth, brain changes triggered by lipopolysaccharides are found to be largely mediated by PKR and might be a valid target to control the production of Aβ and neuroinflammation [281]. Moreover, in an APP/PS1/tau mouse model of AD, a current study has suggested that lixisenatide (i.e., glucagon-like peptide 1 receptor agonists) can reduce neuroinflammation, NFTs, and amyloid plaques [282]. As a result, lixisenatide might be developed as an effective novel treatment for AD [282].…”

Section: Altering the Interplay Of Aβ And Neuroinflammationmentioning

confidence: 80%

Revisiting the Amyloid Cascade Hypothesis: From Anti-Aβ Therapeutics to Auspicious New Ways for Alzheimer’s Disease

Uddin

Kabir

Rahman

et al. 2020

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder related to age, characterized by the cerebral deposition of fibrils, which are made from the amyloid-β (Aβ), a peptide of 40–42 amino acids. The conversion of Aβ into neurotoxic oligomeric, fibrillar, and protofibrillar assemblies is supposed to be the main pathological event in AD. After Aβ accumulation, the clinical symptoms fall out predominantly due to the deficient brain clearance of the peptide. For several years, researchers have attempted to decline the Aβ monomer, oligomer, and aggregate levels, as well as plaques, employing agents that facilitate the reduction of Aβ and antagonize Aβ aggregation, or raise Aβ clearance from brain. Unluckily, broad clinical trials with mild to moderate AD participants have shown that these approaches were unsuccessful. Several clinical trials are running involving patients whose disease is at an early stage, but the preliminary outcomes are not clinically impressive. Many studies have been conducted against oligomers of Aβ which are the utmost neurotoxic molecular species. Trials with monoclonal antibodies directed against Aβ oligomers have exhibited exciting findings. Nevertheless, Aβ oligomers maintain equivalent states in both monomeric and aggregation forms; so, previously administered drugs that precisely decrease Aβ monomer or Aβ plaques ought to have displayed valuable clinical benefits. In this article, Aβ-based therapeutic strategies are discussed and several promising new ways to fight against AD are appraised.

show abstract

Lixisenatide reduces amyloid plaques, neurofibrillary tangles and neuroinflammation in an APP/PS1/tau mouse model of Alzheimer's disease

Cited by 79 publications

References 41 publications

Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer’s Disease patients analyzed by MRI: a retrospective study

Association of impaired fasting glucose and Type 2 Diabetes Mellitus with brain volume changes in Alzheimer’s Disease patients analyzed by MRI: a retrospective study

The novel GLP‐1/GIP analogue DA5‐CH reduces tau phosphorylation and normalizes theta rhythm in the icv. STZ rat model of AD

Revisiting the Amyloid Cascade Hypothesis: From Anti-Aβ Therapeutics to Auspicious New Ways for Alzheimer’s Disease

Contact Info

Product

Resources

About