Is the Use of Proton-pump Inhibitors a Risk Factor for Alzheimer’s Disease? Molecular Mechanisms and Clinical Implications

2018 ◽  
Vol 25 (18) ◽  
pp. 2166-2174 ◽  
Author(s):  
Kazuki Ide ◽  
Norihiro Matsuoka ◽  
Koji Kawakami
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
In Vivo Studies ◽  
Clinical Implications

Proton-pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole, are used for the treatment of gastroesophageal reflux disease and peptic ulcer disease. The use of PPIs has increased, especially in older individuals, and a pharmacoepidemiological study indicated the use of PPIs peaks in people aged 80 years or older. In this population, Alzheimer's disease (AD) is a common neurological disorder and type of dementia, occurring with a frequency of approximately 10%. Currently, over 45 million people are estimated to have dementia worldwide, and it is a major cause of death in the elderly. Recent clinical studies have indicated that chronic use of PPIs can be a risk factor for increased incidence of dementia, including AD. Potential molecular mechanisms related to the pathophysiology of AD (e.g., modulation of amyloid protein processing) have also been reported in both in vitro and in vivo studies. Although the clinical implications of these results are inconclusive, a literature review of the current knowledge is important for future basic and clinical research. This review summarizes the possible mechanisms connecting the use of PPIs and the incidence of AD. Additionally, we summarize results from clinical studies to highlight the influence in humans.

scholarly journals Effects of Tea Catechins on Alzheimer’s Disease: Recent Updates and Perspectives

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2357 ◽  
Author(s):  
Kazuki Ide ◽  
Norihiro Matsuoka ◽  
Hiroshi Yamada ◽  
Daisuke Furushima ◽  
Koji Kawakami
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
In Vivo Studies ◽  
Bioactive Components ◽  
Current Review ◽  
Ad Prevention

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders worldwide. Its incidence is gradually increasing because of an aging demographic. Therefore, AD prevention and modification is important to improve the health status of older adults. Oxidative stress is a component of the pathological mechanisms underlying AD. It is caused by a disruption of the balance between reactive oxygen species and antioxidant molecules. This imbalance also causes neuroinflammation. Catechins, which are bioactive components of tea, have antioxidative and anti-inflammatory effects. Moreover, other potential properties related to AD prevention and modification have been reported in in vitro and in vivo studies. Several clinical studies have also been conducted to date. The current review summarizes recent updates and perspectives of the effects of catechins on AD based on the molecular mechanisms and related clinical studies.

scholarly journals Oxidative Stress in Alzheimer’s Disease: Why Did Antioxidant Therapy Fail?

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Torbjörn Persson ◽  
Bogdan O. Popescu ◽  
Angel Cedazo-Minguez
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Clinical Studies ◽  
Current Knowledge ◽  
The Elderly ◽  
Antioxidant Treatment ◽  
Disease Modifying ◽  
Disease Modifying Treatment

Alzheimer’s disease (AD) is the most common form of dementia in the elderly, with increasing prevalence and no disease-modifying treatment available yet. A remarkable amount of data supports the hypothesis that oxidative stress is an early and important pathogenic operator in AD. However, all clinical studies conducted to date did not prove a clear beneficial effect of antioxidant treatment in AD patients. In the current work, we review the current knowledge about oxidative stress in AD pathogeny and we suggest future paths that are worth to be explored in animal models and clinical studies, in order to get a better approach of oxidative imbalance in this inexorable neurodegenerative disease.

Estrogen and hippocampal synaptic plasticity

2004 ◽  
Vol 1 (4) ◽  
pp. 327-338 ◽  
Author(s):  
MICHAEL FOY ◽  
MICHEL BAUDRY ◽  
RICHARD THOMPSON
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Clinical Studies ◽  
Molecular Mechanisms ◽  
Estrogen Therapy ◽  
Long Term Potentiation ◽  
Neural Function ◽  
Term Potentiation ◽  
Primary Focus

During the past several years, there has been increasing interest in the effects of estrogen on neural function. This enthusiasm is driven, in part, by the results of early clinical studies suggesting that estrogen therapy given after menopause may prevent, or at least delay, the onset of Alzheimer's disease in older women. However, later clinical trials of women with probable Alzheimer's disease had contrary results. Much of the current research related to estrogen and brain function is focused in two directions. One involves clinical studies that examine the potential of estrogen in protecting against cognitive decline during normal aging and against Alzheimer's disease (neuroprotection). The other direction, which is the primary focus of this review, involves laboratory studies that examine the mechanisms by which estrogen can modify the structure of nerve cells and alter the way neurons communicate with other cells in the brain (neuroplasticity). In this review, we examine recent evidence from experimental and clinical research on the rapid effects of estrogen on several mechanisms that involve synaptic plasticity in the nervous system, including hippocampal excitability, long-term potentiation and depression related to sex and aging differences, cellular neuroprotection and probable molecular mechanisms of the action of estrogen in brain tissue.

Long-term use of proton pump inhibitors among community-dwelling persons with and without Alzheimer’s disease

2017 ◽  
Vol 73 (9) ◽  
pp. 1149-1158 ◽  
Author(s):  
Heidi Juntunen ◽  
Heidi Taipale ◽  
Antti Tanskanen ◽  
Anna-Maija Tolppanen ◽  
Jari Tiihonen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Community Dwelling

scholarly journals Boswellic Acids as Promising Leads in Drug Development against Alzheimer’s Disease

2020 ◽  
Vol 27 (1) ◽  
pp. 14-31
Author(s):  
Hossein Haghaei ◽  
Somaieh Soltani ◽  
Seyedrafie Aref Hosseini ◽  
Mohammad Reza Rashidi ◽  
Saeed Karima
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
In Vivo Studies ◽  
Lead Compounds ◽  
Boswellic Acids ◽  
Disease Modifying Agents

Biological activity of Boswellia extract (BE) has been attributed to its main active ingredients; i.e. Boswellic acids (BAs). BE/BAs possess a promising therapeutic potential in neurodegenerative disorders; including Alzheimer's disease (AD). The multifactorial nature of AD pathophysiology necessitates the development of the disease-modifying agents (DMA). Recent multi-targeting approaches for the DMAs development have brought more attention to the plant-derived compounds regarding their better human compatibility because of their biologic origin. This review addresses the current knowledge on the anti-AD activity of BE/BAs based on the available in silico, in vitro, in vivo studies and clinical trials. The contribution of BE/BAs in inflammatory pathways, Tau and β-amyloid proteins, microtubule functions, oxidative stress, cholinesterase and diabetes/insulin pathways involved in AD have been discussed. BAs efficacy in different AD-related pathways has been confirmed in vitro and in vivo. They can be considered as valuable scaffold/lead compounds for multi-targeted DMAs in anti-AD drug discovery and development.

scholarly journals Pyroglutamate Aβ cascade as drug target in Alzheimer’s disease

2021 ◽  
Author(s):  
Thomas A. Bayer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Drug Target ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Passive Immunization ◽  
Model Systems ◽  
Preclinical Model

AbstractOne of the central aims in Alzheimer’s disease (AD) research is the identification of clinically relevant drug targets. A plethora of potential molecular targets work very well in preclinical model systems both in vitro and in vivo in AD mouse models. However, the lack of translation into clinical settings in the AD field is a challenging endeavor. Although it is long known that N-terminally truncated and pyroglutamate-modified Abeta (AβpE3) peptides are abundantly present in the brain of AD patients, form stable and soluble low-molecular weight oligomers, and induce neurodegeneration in AD mouse models, their potential as drug target has not been generally accepted in the past. This situation has dramatically changed with the report that passive immunization with donanemab, an AβpE3-specific antibody, cleared aymloid plaques and stabilized cognitive deficits in a group of patients with mild AD in a phase II trial. This review summarizes the current knowledge on the molecular mechanisms of generation of AβpE, its biochemical properties, and the intervention points as a drug target in AD.

scholarly journals Therapeutic Potential of Mitophagy-Inducing Microflora Metabolite, Urolithin A for Alzheimer’s Disease

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3744
Author(s):  
Dona Pamoda W. Jayatunga ◽  
Eugene Hone ◽  
Harjot Khaira ◽  
Taciana Lunelli ◽  
Harjinder Singh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Therapeutic Benefits ◽  
Urolithin A ◽  
Main Culprit ◽  
Underlying Mechanisms ◽  
Future Therapy

Mitochondrial dysfunction including deficits of mitophagy is seen in aging and neurodegenerative disorders including Alzheimer’s disease (AD). Apart from traditionally targeting amyloid beta (Aβ), the main culprit in AD brains, other approaches include investigating impaired mitochondrial pathways for potential therapeutic benefits against AD. Thus, a future therapy for AD may focus on novel candidates that enhance optimal mitochondrial integrity and turnover. Bioactive food components, known as nutraceuticals, may serve as such agents to combat AD. Urolithin A is an intestinal microbe-derived metabolite of a class of polyphenols, ellagitannins (ETs). Urolithin A is known to exert many health benefits. Its antioxidant, anti-inflammatory, anti-atherogenic, anti-Aβ, and pro-mitophagy properties are increasingly recognized. However, the underlying mechanisms of urolithin A in inducing mitophagy is poorly understood. This review discusses the mitophagy deficits in AD and examines potential molecular mechanisms of its activation. Moreover, the current knowledge of urolithin A is discussed, focusing on its neuroprotective properties and its potential to induce mitophagy. Specifically, this review proposes potential mechanisms by which urolithin A may activate and promote mitophagy.

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