scholarly journals Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Usma Munawara ◽  
Michael Catanzaro ◽  
Weili Xu ◽  
Crystal Tan ◽  
Katsuiku Hirokawa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radical ◽  
Clinical Intervention ◽  
Innate Immune ◽  
Subjective Memory ◽  
Free Radical Production ◽  
Functional Changes ◽  
Radical Production ◽  
Macrophage Populations

Abstract Background Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. Objectives AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. Results We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. Conclusion Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.

Chemiluminescence as an index of drug-induced free radical production in pancreatic islets

Diabetes ◽  
1984 ◽  
Vol 33 (2) ◽  
pp. 160-163 ◽  
Author(s):  
K. Asayama ◽  
D. English ◽  
A. E. Slonim ◽  
I. M. Burr
Keyword(s):  
Free Radical ◽  
Pancreatic Islets ◽  
Drug Induced ◽  
Free Radical Production ◽  
Radical Production

Features of the oxidative status in patients with lupus nephritis

2020 ◽  
Vol 24 (1) ◽  
pp. 39-44
Author(s):  
E. V. Smirnova ◽  
E. V. Proskurnina ◽  
T. N. Krasnova
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Lupus Nephritis ◽  
Blood Plasma ◽  
Respiratory Burst ◽  
Oxidative Status ◽  
Free Radical Production ◽  
Radical Production ◽  
Neutrophil Activity ◽  
Kidney Involvement

BACKGROUND. Oxidative status impairment plays a significant role in the pathogenesis of SLE and lupus nephritis (LN). The data about oxidative status in this disease are incomplete, that’s why it’s necessary to use a new approach to study it. THE AIM: To study oxidative status in SLE patients with kidney involvement. PATIENTS AND METHODS:53 patients with SLE were included in this prospective study, among them 40 patients with different severity of kidney involvement, control group were 87 healthy donors. Oxidative stress parameters were measured: antioxidant activity (AOA) of blood plasma and parameters, characterizing the state of the main source of reactive oxygen species (ROS) – neutrophils, more specifically: specific spontaneous neutrophil activity, specific stimulated activity (peak and integral), coefficient of respiratory burst attenuation, representing the rate of free radical production decrease after stimulation, the higher the value of this parameter, the slower is free radical production decrease. RESULTS. It was shown elevation of neutrophil free radical-producing activity parameters and elevation of blood plasma AOA in patients with LN, comparing to healthy controls. Immunosuppressive therapy with glucocorticosteroids (GCS) and cytostatics (CS) increased blood plasma AOA comparing to monotherapy with GCS. A correlation between oxidative status impairment and intensity of inflammatory reactions was found: correlation of respiratory burst attenuation coefficient with blood sedimentation rate was shown. Reduction of spontaneous free radical-producing neutrophil activity was found in LN patients with NS, which might be the result of neutrophil functional activity attenuation in high disease activity. CONCLUSION. The increased free radical-producing neutrophil activity was shown, which might be the cause of oxidative stress in SLE with LN. It seems warranted investigation of these parameters in samples of larger volume to search targets aimed at neutrophils. The necessity of antioxidant therapy in patients with SLE seems doubtful, as they show significant increase of blood plasma AOA, which might result from compensatory reaction of human organism to oxidative stress and therapy with GCS and CS.

Acetylcholinesterase Inhibitory Potential and Antioxidant Activities of Five Cultivars of Rosa Damascena Mill. From Isparta, Turkey

2020 ◽  
Vol 18 (4) ◽  
pp. 354-359
Author(s):  
Shirin Tarbiat ◽  
Azize Simay Türütoğlu ◽  
Merve Ekingen
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Radical ◽  
Neurodegenerative Disorder ◽  
Antioxidant Activities ◽  
Radical Scavenging ◽  
Acetylcholinesterase Activity ◽  
Rosa Damascena ◽  
Free Radical Damage

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and impairment of language. Alzheimer's disease is strongly associated with oxidative stress and impairment in the cholinergic pathway, which results in decreased levels of acetylcholine in certain areas of the brain. Hence, inhibition of acetylcholinesterase activity has been recognized as an acceptable treatment against Alzheimer's disease. Nature provides an array of bioactive compounds, which may protect against free radical damage and inhibit acetylcholinesterase activity. This study compares the in vitro antioxidant and anticholinesterase activities of hydroalcoholic extracts of five cultivars of Rosa Damascena Mill. petals (R. damascena 'Bulgarica', R. damascena 'Faik', R. damascena 'Iranica', R. damascena 'Complex-635' and R. damascena 'Complex-637') from Isparta, Turkey. The antioxidant activities of the hydroalcoholic extracts were tested for ferric ion reduction and DPPH radical scavenging activities. The anti-acetylcholinesterase activity was also evaluated. All rose cultivars showed a high potency for scavenging free radical and inhibiting acetylcholinesterase activity. There was a significant correlation between antioxidant and acetylcholinesterase inhibitory activity. Among cultivars, Complex-635 showed the highest inhibitory effect with an IC50 value of 3.92 µg/mL. Our results suggest that all these extracts may have the potential to treat Alzheimer's disease with Complex-635 showing more promise.

scholarly journals Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

2016 ◽  
Vol 10 (3) ◽  
pp. 170-177 ◽  
Author(s):  
Adalberto Studart Neto ◽  
Ricardo Nitrini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Clinical Manifestation ◽  
Neurodegenerative Disorder ◽  
Subjective Cognitive Decline ◽  
Subjective Memory ◽  
Increased Risk

ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

Free radical production in the rat retina

1992 ◽  
Vol 55 ◽  
pp. 248
Author(s):  
H. Zhang ◽  
E. Agardh ◽  
C-D. Agardh
Keyword(s):  
Free Radical ◽  
Rat Retina ◽  
Free Radical Production ◽  
Radical Production

Glutamine-induced free radical production in cultured astrocytes

Glia ◽  
2004 ◽  
Vol 46 (3) ◽  
pp. 296-301 ◽  
Author(s):  
Arumugam R. Jayakumar ◽  
K.V. Rama Rao ◽  
Arne Schousboe ◽  
Michael D. Norenberg
Keyword(s):  
Free Radical ◽  
Free Radical Production ◽  
Radical Production ◽  
Cultured Astrocytes

scholarly journals The Innate Immune System in Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Allal Boutajangout ◽  
Thomas Wisniewski
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Innate Immune System ◽  
Late Onset ◽  
Innate Immune ◽  
Amyloid Angiopathy ◽  
Functional Variant ◽  
The Central Nervous System ◽  
Congophilic Amyloid Angiopathy

Alzheimer’s disease (AD) is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloidβ(Aβ) peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA) and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT). Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4) (Potter and Wisniewski (2012), and Verghese et al. (2011)). Recently, it has been reported by two groups independently that a rare functional variant (R47H) of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs) and are the resident macrophages of the central nervous system (CNS). In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD.

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