Intranasal rifampicin for Alzheimer's disease prevention

Umeda, Tomohiro; Tanaka, Akiko; Sakai, Ayumi; Yamamoto, Akira; Sakane, Toshiyasu; Tomiyama, Takami

doi:10.1016/j.trci.2018.06.012

Cited by 29 publications

(25 citation statements)

References 26 publications

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“…Finally, the Osaka mutation provides a useful means to investigate the pathological and physiological roles of Aβ oligomers without the influence of amyloid fibrils or plaques (for example, [75][76][77][78]). Additionally, our model mice harboring this mutation could be a good tool for developing effective approaches in the prevention, treatment, and diagnosis of AD that specifically target Aβ oligomers (for example, [79,80]).…”

Section: Discussionmentioning

confidence: 99%

APP Osaka Mutation in Familial Alzheimer’s Disease—Its Discovery, Phenotypes, and Mechanism of Recessive Inheritance

Tomiyama

Shimada

2020

IJMS

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Alzheimer’s disease is believed to begin with synaptic dysfunction caused by soluble Aβ oligomers. When this oligomer hypothesis was proposed in 2002, there was no direct evidence that Aβ oligomers actually disrupt synaptic function to cause cognitive impairment in humans. In patient brains, both soluble and insoluble Aβ species always coexist, and therefore it is difficult to determine which pathologies are caused by Aβ oligomers and which are caused by amyloid fibrils. Thus, no validity of the oligomer hypothesis was available until the Osaka mutation was discovered. This mutation, which was found in a Japanese pedigree of familial Alzheimer’s disease, is the deletion of codon 693 of APP gene, resulting in mutant Aβ lacking the 22nd glutamate. Only homozygous carriers suffer from dementia. In vitro studies revealed that this mutation has a very unique character that accelerates Aβ oligomerization but does not form amyloid fibrils. Model mice expressing this mutation demonstrated that all pathologies of Alzheimer’s disease can be induced by Aβ oligomers alone. In this review, we describe the story behind the discovery of the Osaka mutation, summarize the mutant’s phenotypes, and propose a mechanism of its recessive inheritance.

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Section: Discussionmentioning

confidence: 99%

APP Osaka Mutation in Familial Alzheimer’s Disease—Its Discovery, Phenotypes, and Mechanism of Recessive Inheritance

Tomiyama

Shimada

2020

IJMS

Self Cite

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“…Additionally, Umeda et. al demonstrated that rifampicin reduced the amount of Aβ deposits, tau phosphorylation, microglial activation, and improved the memory in APP OSK mice (Table 1) [32,33]. Similar to rifampicin, minocycline can also cross the BBB and has anti-bacterial properties along with anti-inflammatory and proteolysis inhibition properties.…”

Section: Gut Microbiota and Admentioning

confidence: 99%

“…Antibiotic treatment and germ-free studies have demonstrated the involvement and importance of gut microbes in AD. Antibiotic treatment in AD mice has been associated with reduced fibril formation, reduced Aβ toxicity, and increased memory and learning [ 30 – 33 ]. Two antibiotics that have been utilized in numerous animal and human studies are rifampicin and minocycline.…”

Section: A Nontraditional View Of Admentioning

confidence: 99%

Microbial involvement in Alzheimer disease development and progression

Bulgart

Neczypor

Wold

et al. 2020

Mol Neurodegeneration

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Alzheimer disease (AD) is the most prominent form of dementia and the 5th leading cause of death in individuals over 65. AD is a complex disease stemming from genetic, environmental, and lifestyle factors. It is known that AD patients have increased levels of senile plaques, neurofibrillary tangles, and neuroinflammation; however, the mechanism(s) by which the plaques, tangles, and neuroinflammation manifest remain elusive. A recent hypothesis has emerged that resident bacterial populations contribute to the development and progression of AD by contributing to neuroinflammation, senile plaque formation, and potentially neurofibrillary tangle accumulation (Fig. 1). This review will highlight recent studies involved in elucidating microbial involvement in AD development and progression.

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“…Even with its many benefits, the oral intake of rifampicin has also been associated with liver injury in humans. To circumvent this limitation, administering rifampicin intranasally or subcutaneously has been suggested [ 147 ]. These routes of rifampicin administration have been shown to be more effective in improving memory than oral administration [ 147 ].…”

Section: Potential Novel Therapeuticsmentioning

confidence: 99%

The Use of Antimicrobial and Antiviral Drugs in Alzheimer’s Disease

Iqbal

Zeng

Pasinetti

2020

IJMS

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The aggregation and accumulation of amyloid-β plaques and tau proteins in the brain have been central characteristics in the pathophysiology of Alzheimer’s disease (AD), making them the focus of most of the research exploring potential therapeutics for this neurodegenerative disease. With success in interventions aimed at depleting amyloid-β peptides being limited at best, a greater understanding of the physiological role of amyloid-β peptides is needed. The development of amyloid-β plaques has been determined to occur 10–20 years prior to AD symptom manifestation, hence earlier interventions might be necessary to address presymptomatic AD. Furthermore, recent studies have suggested that amyloid-β peptides may play a role in innate immunity as an antimicrobial peptide. These findings, coupled with the evidence of pathogens such as viruses and bacteria in AD brains, suggests that the buildup of amyloid-β plaques could be a response to the presence of viruses and bacteria. This has led to the foundation of the antimicrobial hypothesis for AD. The present review will highlight the current understanding of amyloid-β, and the role of bacteria and viruses in AD, and will also explore the therapeutic potential of antimicrobial and antiviral drugs in Alzheimer’s disease.

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Intranasal rifampicin for Alzheimer's disease prevention

Cited by 29 publications

References 26 publications

APP Osaka Mutation in Familial Alzheimer’s Disease—Its Discovery, Phenotypes, and Mechanism of Recessive Inheritance

APP Osaka Mutation in Familial Alzheimer’s Disease—Its Discovery, Phenotypes, and Mechanism of Recessive Inheritance

Microbial involvement in Alzheimer disease development and progression

The Use of Antimicrobial and Antiviral Drugs in Alzheimer’s Disease

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