Anti-Inflammatory Drugs and Risk of Alzheimer's Disease: An Updated Systematic Review and Meta-Analysis

Wang, Jun; Tan, Lan; Wang, Hui-Fu; Tan, Cheng; Meng, Xiangyi; Wang, Chong; Tang, Shaowen; Yu, Jin‐Tai

doi:10.3233/jad-141506

Cited by 220 publications

(137 citation statements)

References 0 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…These proinflammatory molecules could participate in AD pathogenesis either directly, by affecting brain Aβ metabolism (via entry to the CNS through the BBB or neural afferent pathways such as the vagus nerve) 134,135 or indirectly, by affecting Aβ metabolism in the periphery. In this regard, the results of observational studies show that NSAID use is associated with a reduced risk of AD 136 . These findings suggest that chronic systemic inflammation promotes the AD process.…”

Section: Systemic Inflammationmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

Self Cite

View full text Add to dashboard Cite

The global burden of Alzheimer disease (AD), already the most common type of dementia, is expected to increase still further owing to population ageing. AD not only causes severe distress for patients and caregivers, but also results in a large economic burden on society. Current major challenges in AD include the lack of reliable biomarkers for its early diagnosis, as well as the lack of effective preventive strategies and treatments 1,2 . Thus, increased understanding of the molecular patho genesis of AD could lead to the development of improved diagnostic and therapeutic strategies.AD is conventionally regarded as a CNS disorder. However, increasing experimental, epidemiological and clinical evidence has suggested that manifestations of AD extend beyond the brain. These systemic alterations might not be simply secondary effects of the cerebral degeneration seen in AD, but could reflect under lying processes linked to progression of the disease. AD pathogenesis is complex, involving abnormal amyloid-β (Aβ) metabolism, tau hyperphosphorylation, oxidative stress, reactive glial and microglial changes, and other pathological events. Given that Aβ is a major hallmark of AD and a fertile area of research in this disease, this Review focuses on the systemic role of Aβ in AD. We discuss the communication between peripheral and central pools of Aβ, and describe interactions between systemic abnormalities and AD pathogenesis in the brain. We review emerging findings of associations between systemic abnormalities and Aβ metabolism, and describe how these associations might interact with or reflect on the central pathways of Aβ production and clearance. On the basis of these findings, we suggest that interactions between the brain and the periphery might have a crucial role in the development and progression of AD. Aβ biogenesis and catabolismA steady accrual of data from laboratories and clinics is providing increasing support for the concept that an imbalance between the production and clearance of Aβ is a very early (and often initiating) factor in AD 3 . Normal metabolism of Aβ and maintenance of the homeostatic balance between Aβ production and clearance is, therefore, essential to maintain brain health. In fact, physiological metabolism of Aβ occurs not only in the brain but also in the periphery, and communication between these regions is possible (FIG. 1). Central and peripheral production of AβAβ is derived from the proteolytic cleavage of amyloid precursor protein (APP), which is expressed not only in brain cells, including neurons, astrocytes and microglia, but also in peripheral organs and tissues, such as the Abstract | Alzheimer disease (AD) is the most common type of dementia, and is currently incurable; existing treatments for AD produce only a modest amelioration of symptoms. Research into this disease has conventionally focused on the CNS. However, several peripheral and systemic abnormalities are now understood to be linked to AD, and our understanding of how these alterations contribute to AD is becom...

show abstract

Section: Systemic Inflammationmentioning

confidence: 99%

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nonsteroidal anti-inflammatory drugs (NSAIDs ) are well known inhibitors of COX-1 and COX-2. Their involvement in AD has first been suggested by studies which evidenced a reduction of AD risk in patients treated by NSAIDS [24][25][26] . In the majority of organs and tissues, COX-1 is constitutively expressed and COX-2 gene expression is induced especially in case of inflammation.…”

Section: Neuroinflammation and Ad: Role Of Arachidonic Acid And Its Dmentioning

confidence: 98%

“…Despite the data of retrospective epidemiologic studies which reported a lower AD risk in NSAIDStreated populations, randomized controlled trial failed to support the efficiency of these drugs in the AD therapy 26,38 . Therefore, other approaches are needed to explain the discrepancy between the data of the observational studies or the works on AD animal models on one hand and those of the clinical trials on the other hand.…”

mentioning

confidence: 99%

Arachidonic acid in Alzheimer's disease

Olivier¹

2016

J Neurol Neuromedicine

View full text Add to dashboard Cite

Alzheimer's disease is a very complex disease in which neuroinflammation and synaptic dysfunctions play a critical role in association with the two wellknown molecular agents of the disease, the Aβ 1-42 peptide oligomers and the hyperphosphorylated tau protein. Arachidonic acid, the main member of the ω-6 series, is quantitatively the second polyunsaturated fatty acid in brain and is mainly esterified in membrane phospholipids. It is specifically released by the cytosolic phospholipase A 2 whose inhibition or gene suppression counteract the deleterious effects of Aβ 1-42 peptide oligomers on cognitive abilities. Arachidonic acid can be reincorporated under the action of the acylCoA synthetase 4 and lysophospholipid acyltransferases which remain to be characterized. Free arachidonic acid can be involved in Alzheimer's disease through several mechanisms. First it is converted by cyclooxygenases-1/2 and the specific prostaglandin synthases into PGE2 and PGD2 which contributes to the occurrence and progression of neuroinflammation. Neuroinflammation has positive as well as negative effects, by favoring Aβ 1-42 peptide clearance on one hand and by increasing the production of neurotoxic compounds on the other hand. Second, free arachidonic acid is also involved in synaptic functions as a retrograde messenger and as a regulator of neuromediator exocytosis. Third, some studies indicated that free arachidonic acid and its derivatives activate kinases involved in tau hyperphosphorylation. In addition, the dietary intakes of arachidonic acid in western food increased in the last period. Taken together, these various reports support the hypothesis that arachidonic acid is interesting target in nutrition-based preventive strategies against this disease.

show abstract

“…Применение нестероидных противовоспалительных средств (НПВС), по данным нескольких метаанализов, ассоциируется со снижением частоты развития деменции [34,35]. Однако многоцентровые плацебо-контролируе-мые исследования не показали эффективности НПВС (при значительном увеличении числа нежелательных, преимущественно желудочно-кишечных осложнений), в частности напроксена (220 мг три раза в день) или целе-коксиба (200 мг два раза в сутки) [36].…”

Section: профилактика ба на основе лекарственных средствunclassified

Management of Patients With Alzheimer’s Disease

Парфенов¹,

Кабаева²

2018

Med. sov.

View full text Add to dashboard Cite

Anti-Inflammatory Drugs and Risk of Alzheimer's Disease: An Updated Systematic Review and Meta-Analysis

Cited by 220 publications

References 0 publications

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

A systemic view of Alzheimer disease — insights from amyloid-β metabolism beyond the brain

Arachidonic acid in Alzheimer's disease

Management of Patients With Alzheimer’s Disease

Contact Info

Product

Resources

About