Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion |
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| Affiliation: | 2. Department of Cardiovascular Surgery, National Cerebral and Cardiovascular Center, Suita, Osaka 565-8565, Japan;2. Department of Neurology, the Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China;3. Department of Neurology, the Second Affiliated Hospital and Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China;4. Department of Neurology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China;5. Department of Neurology, the Affiliated Wenling Hospital of Wenzhou Medical University, Wenling, Zhejiang, China;2. Department of Hematology and Oncology, Tufts Medical Center, Boston, Massachusetts;3. Department of Neurology & Neurotherapeutics, University of Texas Southwestern, Dallas, Texas;2. UPMC Stroke Institute, Departments of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;3. UPMC Stroke Institute, Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, New Yark |
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| Abstract: | BackgroundMultiple 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.MethodsAPP23 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.ResultsIn 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.ConclusionsThe present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion. |
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