Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease

This review aims to provide scientific evidence of the role of oxidative stress in the development of cognitive impairment and its progression to Alzheimer's disease. Oxidative stress originates when there is an uncontrolled production of free radicals that disrupts the balance between oxidants and antioxidants, favoring oxidants. It has been associated with oxidative stress with the pathogenesis of brain aging, cognitive impairment and some neurological diseases. The cells of the central nervous system produce a high amount of free radicals since their energy demand is high, this coupled with a low antioxidant capacity, favors the appearance of a pro-oxidant environment that contributes to neurodegeneration and neuronal death. Alzheimer's disease is the most frequent form of dementia, it is characterized by neurodegenerative changes that occur with cognitive impairment, progressive impairment of memory and thought, until preventing the performance of daily life activities. Neuropathologically, it is characterized by the presence of extracellular deposits of β-amyloid peptide in the form of neurofibrillar plaques and clews; lesions capable of generating damage and neuronal death that lead to cognitive failure through the generation of more free radicals

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Elevated oxidative stress in models of normal brain aging and Alzheimer's disease

Life Sciences ◽

10.1016/s0024-3205(99)00442-7 ◽

1999 ◽

Vol 65 (18-19) ◽

pp. 1883-1892 ◽

Cited By ~ 97

Author(s):

D.Allan Butterfield ◽

Beverly Howard ◽

Servet Yatin ◽

Tanuja Koppal ◽

Jennifer Drake ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Aging ◽

Normal Brain

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Association Between Oxidative Stress and Altered Cholesterol Metabolism in Alzheimer’s Disease Patients

Current Alzheimer Research ◽

10.2174/1567205017666201203123046 ◽

2020 ◽

Vol 17 ◽

Author(s):

Amira Zarrouk ◽

Souha Hammouda ◽

Imen Ghzaiel ◽

Sonia Hammami ◽

Wided Khamlaoui ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cholesterol Metabolism ◽

Plasma Cholesterol ◽

Redox Homeostasis ◽

Binary Logistic Regression ◽

Cholesterol Oxidation ◽

Antioxidant Enzyme Activities ◽

Gpx Activity

Objective: Oxidative stress is the main feature of several diseases including Alzheimer’s disease (AD). The involvement of oxysterols derivates has been recently reported. In this study, the implication of oxidative stress in cholesterol impairment in AD patients will be evaluated. Methods: A case-control study was conducted on 56 AD patients and 97 controls. Levels of oxidative biomarkers, including lipid peroxidation products and antioxidant enzyme activities were measured with spectrophotometric methods on red blood cells (RBCs) and plasma. Cholesterol precursors and oxysterols (7KC, 7α-OHC, 7β-OHC, 24S-OH, 27-OHC, and 25-OHC) in plasma were quantified by gas chromatography coupled with mass spectrometry. In RBCs and plasma of AD patients, a significant decrease of glutathione peroxidase (GPx) activity was detected associated with raised levels of malondialdehyde (MDA). A decreased level of lanosterol and an accumulation of 7β-OHC, 24S-OHC, 27-OHC, and 25-OHC that were higher in plasma of AD patients, compared to controls, were also observed in AD patients. Conclusion: Mini-Mental State Examination (MMSE) score was correlated with MDA and conjugated dienes (CD) levels in plasma. Besides, the MDA level in RBCs was correlated with 7βhydroxycholesterol (7β-OHC). Binary logistic regression revealed an association between GPx activity and AD (OR=0.895, 95%CI: 0.848-0.945; P<0.001). Our data consolidate the relationship between the rupture of redox homeostasis and lipid and cholesterol oxidation in AD.

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Cholesterol Metabolism and Oxidative Stress in Alzheimer’s Disease

Studies on Alzheimer's Disease - Oxidative Stress in Applied Basic Research and Clinical Practice ◽

10.1007/978-1-62703-598-9_9 ◽

2013 ◽

pp. 119-135

Author(s):

Luigi Iuliano ◽

Valerio Leoni

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cholesterol Metabolism ◽

And Oxidative Stress

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Micronutrients and Alzheimer's disease

Proceedings of The Nutrition Society ◽

10.1079/pns2005459 ◽

2005 ◽

Vol 64 (4) ◽

pp. 565-570 ◽

Cited By ~ 27

Author(s):

Hannes B. Staehelin

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Fruits And Vegetables ◽

Brain Aging ◽

Model Systems ◽

Bioactive Substances ◽

Balanced Diet ◽

Key Factor ◽

Major Factors

The current high life expectancy is overshadowed by neurodegenerative illnesses that lead to dementia and dependence. Alzheimer's disease (AD) is the most common of these conditions, and is considered to be a proteinopathy, with amyloid-β42 as a key factor, leading via a cascade of events to neurodegeneration. Major factors involved are oxidative stress, perturbed Ca homeostasis and impaired energy metabolism. Protection against oxidative stress by micronutrients (including secondary bioactive substances) has been shown in transgenic Alzheimer model systems to delay AD. Epidemiological evidence is less conclusive, but the vast majority of the evidence supports a protective effect on cognitive functions in old age and AD. Thus, a diet rich in fruits and vegetables but also containing meat and fish is the most suitable to provide adequate micronutrients. The strong link between cardiovascular risk and AD may be explained by common pathogenetic mechanisms mediated, for example, by homocysteine and thus dependant on B-vitamins (folate and vitamins B12 and B6). However, micronutrients may also be harmful. The high affinity of amyloid for metals (Fe, Al and Zn) favours the generation of reactive oxygen species and triggers an inflammatory response. Micronutrients in a balanced diet have a long-lasting, albeit low, protective impact on brain aging, hence prevention should be life long.

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Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽

10.1024/1662-9647/a000074 ◽

2012 ◽

Vol 25 (4) ◽

pp. 235-245 ◽

Cited By ~ 64

Author(s):

Katja Franke ◽

Christian Gaser

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Healthy Aging ◽

Brain Aging ◽

Elderly Subjects ◽

Additional Increase ◽

Longitudinal Changes ◽

Novel Method ◽

The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

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