Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion.

Abstract

BACKGROUND:

Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-β accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood.

METHODS:

APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry.

RESULTS:

In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-β plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-β pathology and neuronal loss, alleviated neuroinflammation and oxidative stress.

CONCLUSIONS:

The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion.

• Authors: Xia Liu, Toru Yamashita, Jingwei Shang, Xiaowen Shi, Ryuta Morihara, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 28 Issue 7 Pg. 1993-2002 (Jul 2019) ISSN: 1532-8511 [Electronic] United States
• PMID: 31029568 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• APP protein, human
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Anti-Inflammatory Agents
• Antioxidants
• Inflammation Mediators
• Neuroprotective Agents
• Twendee X
• Glutamine
• Cystine
• Ascorbic Acid

Topics

• Alzheimer Disease (drug therapy, genetics, pathology, physiopathology)
• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (genetics)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Ascorbic Acid (administration & dosage, pharmacology)
• Behavior, Animal (drug effects)
• Brain (drug effects, pathology, physiopathology)
• Cerebrovascular Circulation (drug effects)
• Cerebrovascular Disorders (drug therapy, pathology, physiopathology)
• Chronic Disease
• Cognition (drug effects)
• Cystine (administration & dosage, pharmacology)
• Dietary Supplements
• Disease Models, Animal
• Female
• Glutamine (administration & dosage, pharmacology)
• Inflammation Mediators (metabolism)
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Motor Activity (drug effects)
• Mutation
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Plaque, Amyloid