An Isoquinolinium Dual Inhibitor of Cholinesterases and Amyloid β Aggregation Mitigates Neuropathological Changes in a Triple-Transgenic Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 11 (20) ◽  
pp. 3346-3357
Author(s):  
Yaojun Ju ◽  
Harapriya Chakravarty ◽  
Kin Yip Tam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Amyloid Β ◽  
Transgenic Mouse Model ◽  
Dual Inhibitor ◽  
Model Of Alzheimer’S Disease ◽  
Triple Transgenic Mouse

scholarly journals Tetrahydrobiopterin Improves Recognition Memory in the Triple-Transgenic Mouse Model of Alzheimer’s Disease, Without Altering Amyloid-β and Tau Pathologies

2020 ◽  
pp. 1-19
Author(s):  
Hortense Fanet ◽  
Marine Tournissac ◽  
Manon Leclerc ◽  
Vicky Caron ◽  
Cyntia Tremblay ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Metabolic Disorders ◽  
Amyloid Β ◽  
Transgenic Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Triple Transgenic Mouse

Background: Alzheimer’s disease (AD) is a multifactorial disease, implying that multi-target treatments may be necessary to effectively cure AD. Tetrahydrobiopterin (BH4) is an enzymatic cofactor required for the synthesis of monoamines and nitric oxide that also exerts antioxidant and anti-inflammatory effects. Despite its crucial role in the CNS, the potential of BH4 as a treatment in AD has never been scrutinized. Objective: Here, we investigated whether BH4 peripheral administration improves cognitive symptoms and AD neuropathology in triple-transgenic mouse model of AD (3xTg-AD) mice, a model of age-related tau and amyloid-β (Aβ) neuropathologies associated with behavior impairment. Methods: Non-transgenic (NonTg) and 3xTg-AD mice were subjected to a control diet (5% fat – CD) or to a high-fat diet (35% fat - HFD) from 6 to 13 months to exacerbate metabolic disorders. Then, mice received either BH4 (15 mg/kg/day, i.p.) or vehicle for ten consecutive days. Results: This sub-chronic administration of BH4 rescued memory impairment in 13-month-old 3xTg-AD mice, as determined using the novel object recognition test. Moreover, the HFD-induced glucose intolerance was completely reversed by the BH4 treatment in 3xTg-AD mice. However, the HFD or BH4 treatment had no significant impact on Aβ and tau neuropathologies. Conclusion: Overall, our data suggest a potential benefit from BH4 administration against AD cognitive and metabolic symptoms accentuated by HFD consumption in 3xTg-AD mice, without altering classical neuropathology. Therefore, BH4 should be considered as a candidate for drug repurposing, at least in subtypes of cognitively impaired patients experiencing metabolic disorders.

P1-081: Memantine reduces amyloid and Tau pathologies in a triple-transgenic mouse model of Alzheimer's disease

2008 ◽  
Vol 4 ◽  
pp. T230-T230
Author(s):  
Kim N. Green ◽  
Hilda Martinez-Coria ◽  
Pradeep K. Banerjee ◽  
Sandeep Gupta ◽  
Frank M. LaFerla
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Triple Transgenic Mouse

scholarly journals Retinal macroglia changes in a triple transgenic mouse model of Alzheimer's disease

2014 ◽  
Vol 127 ◽  
pp. 252-260 ◽  
Author(s):  
Malia M. Edwards ◽  
José J. Rodríguez ◽  
Raquel Gutierrez-Lanza ◽  
Joseph Yates ◽  
Alexei Verkhratsky ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Transgenic Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Triple Transgenic Mouse
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