The Association between the Usage of Non-Steroidal Anti-Inflammatory Drugs and Cognitive Status: Analysis of Longitudinal and Cross-Sectional Studies from the Global Alzheimer’s Association Interactive Network and Transcriptomic Data

The degenerative cognitive and physical decline of Alzheimer patients, coupled with the extensive psychological and economic tolls imposed on family members that serve as caretakers, necessitate the discovery of effective cures and preventative measures for age-related cognitive depreciation. In the journey of Alzheimer’s disease treatment discovery, several cross-sectional and longitudinal studies have delineated a noticeable association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs), a class of low-cost drugs with minimal side effects, and the alleviation of age-related memory impairment. In this study, four datasets (two cross-sectional and two longitudinal studies) derived from the Global Alzheimer’s Association Interactive Network (GAAIN) were analyzed. The significant association between the usage of NSAIDs and better cognitive status was observed. The results agree with the findings of previous studies that the use of NSAIDs may be beneficial in the early stages of Alzheimer’s disease. Transcriptomic data show that ibuprofen treatment results in upregulation of several genes involved in arachidonic acid metabolism including PPARγ, Cyp4a12b, Cyp2c66, and Cyp2c37 in the hippocampus. The increase in conversion of arachidonic acid into anti-inflammatory 16C and 18C dicarboxylic acids as well as epoxyeicosatrienoic acids may play a role in reducing the risk of Alzheimer’s disease development.

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Emerging Promise of Immunotherapy for Alzheimer’s Disease: A New Hope for the Development of Alzheimer’s Vaccine

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200422105156 ◽

2020 ◽

Vol 20 (13) ◽

pp. 1214-1234 ◽

Cited By ~ 4

Author(s):

Md. Tanvir Kabir ◽

Md. Sahab Uddin ◽

Bijo Mathew ◽

Pankoj Kumar Das ◽

Asma Perveen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune Response ◽

Neutralizing Antibodies ◽

Neurodegenerative Disorder ◽

Symptomatic Relief ◽

Aβ Oligomers ◽

Th2 Immune Response ◽

Age Related ◽

Anti Inflammatory

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.

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The potential role of non-steroidal anti-inflammatory drugs in treating Alzheimer’s disease

Expert Opinion on Investigational Drugs ◽

10.1517/13543784.13.11.1469 ◽

2004 ◽

Vol 13 (11) ◽

pp. 1469-1481 ◽

Cited By ~ 31

Author(s):

Bruno P Imbimbo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Potential Role ◽

Inflammatory Drugs ◽

Anti Inflammatory

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Immune modulations and immunotherapies for Alzheimer’s disease: a comprehensive review

Reviews in the Neurosciences ◽

10.1515/revneuro-2021-0092 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Sara Mahdiabadi ◽

Sara Momtazmanesh ◽

George Perry ◽

Nima Rezaei

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Β ◽

Cognitive Outcomes ◽

Tau Proteins ◽

Causal Role ◽

Wide Range ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Immune Related Genes

Abstract Alzheimer’s disease (AD), the most common cause of dementia, is characterized by progressive cognitive and memory impairment ensued from neuronal dysfunction and eventual death. Intraneuronal deposition of tau proteins and extracellular senile amyloid-β plaques have ruled as the supreme postulations of AD for a relatively long time, and accordingly, a wide range of therapeutics, especially immunotherapies have been implemented. However, none of them resulted in significant positive cognitive outcomes. Especially, the repetitive failure of anti-amyloid therapies proves the inefficiency of the amyloid cascade hypothesis, suggesting that it is time to reconsider this hypothesis. Thus, for the time being, the focus is being shifted to neuroinflammation as a third core pathology in AD. Neuroinflammation was previously considered a result of the two aforementioned phenomena, but new studies suggest that it might play a causal role in the pathogenesis of AD. Neuroinflammation can act as a double-edged sword in the pathogenesis of AD, and the activation of glial cells is indispensable for mediating such attenuating or detrimental effects. The association of immune-related genes polymorphisms with the clinical phenotype of AD as well as the protective effect of anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs supports the possible causal role of neuroinflammation in AD. Here, we comprehensively review immune-based therapeutic approaches toward AD, including monoclonal antibodies and vaccines. We also discuss their efficacy and underlying reasons for shortcomings. Lastly, we highlight the capacity of modulating the neuroimmune interactions and targeting neuroinflammation as a promising opportunity for finding optimal treatments for AD.

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