The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer’s Disease

Calsolaro, Valeria; Antognoli, Rachele; Okoye, Chukwuma; Monzani, Fabio

doi:10.3389/fphar.2019.01465

Cited by 51 publications

(38 citation statements)

References 44 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dementia affects more than 50 million people today [ 6 ]. Especially AD, which accounts for most dementia cases [ 7 ], still lacks appropriate medical interventions to treat or prevent the ongoing neurodegenerative processes. In the current study, a knock-in mouse model for AD was used, which simulates amyloid-β (Aβ) pathology that is one of the most prominent hallmarks of the complex disease [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Nieraad

Bruin

Arne

et al. 2021

IJMS

View full text Add to dashboard Cite

Hyperhomocysteinemia has been suggested potentially to contribute to a variety of pathologies, such as Alzheimer’s disease (AD). While the impact of hyperhomocysteinemia on AD has been investigated extensively, there are scarce data on the effect of AD on hyperhomocysteinemia. The aim of this in vivo study was to investigate the kinetics of homocysteine (HCys) and homocysteic acid (HCA) and effects of AD-like pathology on the endogenous levels. The mice received a B-vitamin deficient diet for eight weeks, followed by the return to a balanced control diet for another eight weeks. Serum, urine, and brain tissues of AppNL-G-F knock-in and C57BL/6J wild type mice were analyzed for HCys and HCA using LC-MS/MS methods. Hyperhomocysteinemic levels were found in wild type and knock-in mice due to the consumption of the deficient diet for eight weeks, followed by a rapid normalization of the levels after the return to control chow. Hyperhomocysteinemic AppNL-G-F mice had significantly higher HCys in all matrices, but not HCA, compared to wild type control. Higher serum concentrations were associated with elevated levels in both the brain and in urine. Our findings confirm a significant impact of AD-like pathology on hyperhomocysteinemia in the AppNL-G-F mouse model. The immediate normalization of HCys and HCA after the supply of B-vitamins strengthens the idea of a B-vitamin intervention as a potentially preventive treatment option for HCys-related disorders such as AD.

show abstract

Section: Introductionmentioning

confidence: 99%

Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Nieraad

Bruin

Arne

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…In 2019 more than 50 million people were affected by dementia and the number could increase to about 152 million by 2050 [ 1 ]. Alzheimer’s disease (AD) is the most common type of dementia, accounting for 2/3 of all cases [ 2 ]. More than 400 failures in drug development during the last decades [ 3 ] have led to the consideration of alternative intervention options, e.g., repurposing, combinatory approaches and preventive treatments [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease

et al. 2020

View full text Add to dashboard Cite

Background: Hyperhomocysteinemia is considered a possible contributor to the complex pathology of Alzheimer’s disease (AD). For years, researchers in this field have discussed the apparent detrimental effects of the endogenous amino acid homocysteine in the brain. In this study, the roles of hyperhomocysteinemia driven by vitamin B deficiency, as well as potentially beneficial dietary interventions, were investigated in the novel AppNL-G-F knock-in mouse model for AD, simulating an early stage of the disease. Methods: Urine and serum samples were analyzed using a validated LC-MS/MS method and the impact of different experimental diets on cognitive performance was studied in a comprehensive behavioral test battery. Finally, we analyzed brain samples immunohistochemically in order to assess amyloid-β (Aβ) plaque deposition. Results: Behavioral testing data indicated subtle cognitive deficits in AppNL-G-F compared to C57BL/6J wild type mice. Elevation of homocysteine and homocysteic acid, as well as counteracting dietary interventions, mostly did not result in significant effects on learning and memory performance, nor in a modified Aβ plaque deposition in 35-week-old AppNL-G-F mice. Conclusion: Despite prominent Aβ plaque deposition, the AppNL-G-F model merely displays a very mild AD-like phenotype at the investigated age. Older AppNL-G-F mice should be tested in order to further investigate potential effects of hyperhomocysteinemia and dietary interventions.

show abstract

“…Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders ( Calsolaro et al., 2019 ). The histopathology of AD includes two major hallmarks namely amyloid plaques (Aβ) and neurofibrillary tangles consisting of highly phosphorylated protein tau (p-tau) ( Deture and Dickson, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective activity of Ulmus pumila L. in Alzheimer's disease in rats; role of neurotrophic factors

Hussein

Afifi

Soliman

et al. 2020

Heliyon

View full text Add to dashboard Cite

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders which affects the hippocampus and cortical neurons leading to impairment of cognitive ability. Treatment of AD depends mainly on acetylcholinesterase inhibitors, however, a novel therapeutic approach is introduced based on the maintenance of neuronal viability and functionality exerted through neurotrophic factors. In the current study, Ulmus pumila L. leaves alcoholic extract was investigated for its neuroprotective activity in AlCl 3 -induced AD in rats. Rats were orally treated with AlCl 3 (17 mg/kg) for 4 weeks followed by U. pumila extract (150 mg/kg b.wt.) for another 6 weeks. Treatment of neuro-intoxicated rats with U. pumila extract resulted in a significant regulation in neurotrophic factors; brain derived neurotrophic factor and transforming growth factor-β and pro-inflammatory cytokine; TNF. It also induced an elevation in serum levels of monoamine neurotransmitters; norepinephrine, dopamine and serotonin and a decline in brain acetlycholinesterase activity. U. pumila extract also showed potent antioxidant activity as indicated by the declined malondialdehyde and elevated reduced glutathione, catalase and super oxide dismutase levels in AD rats‘ brains. Histological improvement was detected in the cerebral cortex, the hippocampus and striatum of the treated rats . The phytochemical analysis of U. pumila extract revealed high contents of flavonoids and phenolics and the major compounds were isolated and chemically characterized. Additionally, U. pumila extract and the isolated compounds exerted a prominent activity in in-vitro acetylcholinesterase inhibition assay with kaempferol-3-O-β-glucoside being the most potent compound showing IC 50 of 29.03 ± 0.0155 μM. A molecular docking study indicated high affinity of kaempferol-3-O-β-robinobioside on acetylcholine esterase binding site with estimated binding free energy of –8.26 kcal/mol.

show abstract

The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer’s Disease

Cited by 51 publications

References 44 publications

Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Effects of Alzheimer-Like Pathology on Homocysteine and Homocysteic Acid Levels—An Exploratory In Vivo Kinetic Study

Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease

Neuroprotective activity of Ulmus pumila L. in Alzheimer's disease in rats; role of neurotrophic factors

Contact Info

Product

Resources

About