Oxidative Challenge in Alzheimer's Disease: State of Knowledge and Future Needs

Cervellati, Carlo; Wood, Paul L.; Romani, Arianna; Valacchi, Giuseppe; Squerzanti, Monica; Sanz, Juana María; Ortolani, Beatrice; Zuliani, Giovanni

doi:10.1136/jim-2015-000017

Cited by 69 publications

(97 citation statements)

References 163 publications

(427 reference statements)

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“…In the Italian subsample, COMT rs174696 was also associated with depression, partially supporting our hypothesis about oxidative stress. Indeed, COMT alterations may lead to an imbalance of monoamine levels (including serotonin) which, in turn, may lead to the development of a depressive phenotype, maybe through the increase of the oxidative stress [50]. However, this association was not replicated in our total sample or in the Greek subsample.…”

Section: Discussioncontrasting

confidence: 50%

“…Finally, our exploratory analysis on serologic parameters related to inflammation and oxidative stress processes (performed only in the Greek subsample) showed some nominal associations with the variants investigated. Taking into account that impairment of these 2 processes has been linked with both LOAD [50, 51] and depression [52, 53], this may point at a partial common genetic background between LOAD and depression [54]. Obviously, further studies are needed to confirm these hypotheses, particularly when considering the exploratory nature of these analyses.…”

Section: Discussionmentioning

confidence: 99%

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Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

et al. 2019

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Background: Alzheimer’s disease (AD) is a neurodegenerative disorder accounting for 60–70% of dementia cases. Genetic origin accounts for 49–79% of disease risk. This paper aims to investigate the association of 17 polymorphisms within 7 genes involved in neurotransmission (COMT, HTR2A, PPP3CC, RORA, SIGMAR1, SIRT1, and SORBS3) and AD. Methods: A Greek and an Italian sample were investigated, for a total of 156 AD subjects and 301 healthy controls. Exploratory analyses on psychosis and depression comorbidities were performed, as well as on other available clinical and serological parameters. Results: AD was associated with rs4680 within the COMT gene in the total sample. Trends of association were found in the 2 subsamples. Some nominal associations were found for the depressive phenotype. rs10997871 and rs10997875 within SIRT1 were nominally associated with depression in the total sample and in the Greek subsample. rs174696 within COMT was associated with depression comorbidity in the Italian subsample. Discussion: Our data support the role of COMT, and particularly of rs4680, in the pathogenesis of AD. Furthermore, the SIRT1 gene seems to modulate depressive symptomatology in the AD population.

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Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

et al. 2019

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“…151,152 Ab deposits and activated microglia and astrocytes are major sources of reactive oxygen species (ROS) in early AD. 153 Among the numerous harmful effects of ROS overproduction, mitochondrial dysfunction contributes to energy imbalance and apoptosis of nerve cells.…”

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confidence: 99%

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Манухина

Downey

Shi

et al. 2016

Exp Biol Med (Maywood)

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Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso-and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

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“…There have been some reports of antioxidants showing some efficacy in few clinical trials, but these studies have not been able to answer whether antioxidants are truly protective against AD [78,79] . A randomized clinical trial has shown that treatment with α-tocopherol at a dose of 2000 IU/d reduces neuronal damage and slows the progression of AD in patients with moderately severe impairment [79,80] .…”

Section: Antioxidantsmentioning

confidence: 99%

Management of Alzheimers Disease: Role of Existing Therapies, Traditional Medicines and New Treatment Targets

Malve¹

2017

ijps

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Oxidative Challenge in Alzheimer's Disease: State of Knowledge and Future Needs

Cited by 69 publications

References 163 publications

Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

Alzheimer’s Disease and Neurotransmission Gene Variants: Focus on Their Effects on Psychiatric Comorbidities and Inflammatory Parameters

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Management of Alzheimers Disease: Role of Existing Therapies, Traditional Medicines and New Treatment Targets

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