Microbial involvement in Alzheimer disease development and progression

Bulgart, Hannah R.; Neczypor, Evan W; Wold, Loren E.; Mackos, Amy R.

doi:10.1186/s13024-020-00378-4

Cited by 76 publications

(74 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The infection hypothesis was proposed decades ago when it became clear that there should be some triggering events at some points of the disease progression. 7 , 145–147 It is noteworthy that Oskar Fisher, in the same epoch as Alois Alzheimer, had already evoked this possibility. 148 Early evidence was done on HSV-1 viruses.…”

Section: Experimental Data Substantially Support the Infection Hypothesis Of Admentioning

confidence: 99%

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most common form of dementia and aging is the most common risk factor for developing the disease. The etiology of AD is not known but AD may be considered as a clinical syndrome with multiple causal pathways contributing to it. The amyloid cascade hypothesis, claiming that excess production or reduced clearance of amyloid-beta (Aβ) and its aggregation into amyloid plaques, was accepted for a long time as the main cause of AD. However, many studies showed that Aβ is a frequent consequence of many challenges/pathologic processes occurring in the brain for decades. A key factor, sustained by experimental data, is that low-grade infection leading to production and deposition of Aβ, which has antimicrobial activity, precedes the development of clinically apparent AD. This infection is chronic, low grade, largely clinically silent for decades because of a nearly efficient antimicrobial immune response in the brain. A chronic inflammatory state is induced that results in neurodegeneration. Interventions that appear to prevent, retard or mitigate the development of AD also appear to modify the disease. In this review, we conceptualize further that the changes in the brain antimicrobial immune response during aging and especially in AD sufferers serve as a foundation that could lead to improved treatment strategies for preventing or decreasing the progression of AD in a disease-modifying treatment.

show abstract

Section: Experimental Data Substantially Support the Infection Hypothesis Of Admentioning

confidence: 99%

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Fülöp¹,

Tripathi²,

Rodrigues³

et al. 2021

NDT

View full text Add to dashboard Cite

show abstract

“…There are little approved treatments can reverse or prevent the development of this disease ( Scheltens et al, 2016 ; Hodson, 2018 ; Long and Holtzman, 2019 ). The pathological feature of AD is abnormal folding and deposition of amyloid plaques (Amyloid β, Aβ) leads to formation of senile plaque (SP), and the accumulation of tau protein leads to neurofibrillary tangles (NFT) ( Simard et al, 2006 ; Bulgart et al, 2020 ). Aβ 42 fibrils is a major component of amyloid plaques and appears central to AD pathogenesis ( Fagan et al, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

A Novel Nanosystem Realizing Curcumin Delivery Based on Fe3O4@Carbon Dots Nanocomposite for Alzheimer’s Disease Therapy

Kuang

Zhang

Xiong

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the most common neurodegenerative disease, which seriously affects human health but lacks effective treatment methods. Amyloid β (Aβ) aggregates are considered a possible target for AD treatment. Evidence is increasingly showing that curcumin (CUR) can partly protect cells from Aβ-mediated neurotoxicity by inhibiting Aβ aggregation. However, the efficiency of targeted cellular uptake and bioavailability of CUR is very low due to its poor stability and water-solubility. In order to better improve the cell uptake efficiency and bioavailability of CUR and reduce the cytotoxicity of high-dose CUR, a novel CUR delivery system for AD therapy has been constructed based on the employment of the Fe3O4@carbon dots nanocomposite (Fe3O4@CDs) as the carrier. CUR-Fe3O4@CDs have a strong affinity toward Aβ and effectively inhibit extracellular Aβ fibrillation. In addition, CUR-Fe3O4@CDs can inhibit the production of reactive oxygen species (ROS) mediated by Aβ fibrils and the corresponding neurotoxicity in PC12 cells. More importantly, it can restore nerve damage and maintained neuronal morphology. These results indicate that the application of CUR-Fe3O4@CDs provides a promising platform for the treatment of AD.

show abstract

“…In terms of direct effects, pathogenic oral microbes affect the occurrence of AD by entering the brain tissue through different paths and directly damaging the CNS (Parahitiyawa et al, 2009;Teixeira et al, 2017;Bulgart et al, 2020). Hemorrhagic oral treatment such as tooth extraction or transient bacteremia caused by gingivitis and periodontitis allows pathogenic microorganisms to break through the oral mucosal barrier and invade the bloodstream.…”

Section: The Direct Effect Of Oral Microbes On Admentioning

confidence: 99%

“…Oral microorganisms can also enter the brain through the trigeminal nerve, which are connected to the brain (Teixeira et al, 2017). Microbes entering the brain tissue and the pro-inflammatory factors they released further trigger an immune cascade, which includes the activation of microglia, inflammatory responses, and the activation of the complement system (Bulgart et al, 2020). Studies have also suggested that Aβ protein, which functions as an antibacterial peptide in innate immunity, may inhibit neuroinflammation to a certain extent and play a protective role in the brain.…”

Section: The Direct Effect Of Oral Microbes On Admentioning

confidence: 99%

The Oral-Gut-Brain AXIS: The Influence of Microbes in Alzheimer’s Disease

Narengaowa

Kong

Lan

et al. 2021

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is one of the most frequently diagnosed neurodegenerative disorders worldwide and poses a major challenge for both affected individuals and their caregivers. AD is a progressive neurological disorder associated with high rates of brain atrophy. Despite its durable influence on human health, understanding AD has been complicated by its enigmatic and multifactorial nature. Neurofibrillary tangles and the deposition of amyloid-beta (Aβ) protein are typical pathological features and fundamental causes of cognitive impairment in AD patients. Dysbiosis of oral and gut microbiota has been reported to induce and accelerate the formation of Aβ plaques and neurofibrillary tangles. For instance, some oral microbes can spread to the brain through cranial nerves or cellular infections, which has been suggested to increase the risk of developing AD. Importantly, the interaction between intestinal microbiota and brain cells has been recognized as influencing the development of AD as well as other neurodegenerative diseases. In particular, the metabolites produced by certain intestinal microorganisms can affect the activity of microglia and further mediate neuroinflammation, which is a leading cause of neuronal necrosis and AD pathogenesis. Which pathogens and associated pathways are involved in the development and progression of AD remains to be elucidated; however, it is well-known that gut microbiota and their metabolites can affect the brain by both direct and indirect means. Understanding the specific mechanisms involved in the interaction between these pathogens and the nervous system is vital for the early intervention in AD. In this review, we aim to comprehensively discuss the possible mechanistic pathways underlying the oral-brain, the gut-brain and the oral-gut-brain associations.

show abstract

Microbial involvement in Alzheimer disease development and progression

Cited by 76 publications

References 126 publications

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

Targeting Impaired Antimicrobial Immunity in the Brain for the Treatment of Alzheimer’s Disease

A Novel Nanosystem Realizing Curcumin Delivery Based on Fe3O4@Carbon Dots Nanocomposite for Alzheimer’s Disease Therapy

The Oral-Gut-Brain AXIS: The Influence of Microbes in Alzheimer’s Disease

Contact Info

Product

Resources

About