Emerging roles of pathogens in Alzheimer disease

Miklóssy, Judith

doi:10.1017/s1462399411002006

Cited by 170 publications

(157 citation statements)

References 344 publications

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“…The majority of pathological changes in AD patients, including inflammation, brain atrophy, immune abnormalities, amyloid formation, changes of gene expression and cognitive impairment, are all considered to be associated with microbial infections (Bhattacharjee and Lukiw, 2013;Heintz and Mair, 2014;Huang et al, 2014;Mancuso et al, 2014;Miklossy, 2011). Gut microbiota and host form the complex of mutualistic symbiosis in normal conditions and the symbiotic environment can effectively suppress the infection of potential pathogenic microorganisms.…”

Section: Microbial Infection and Admentioning

confidence: 99%

Alzheimer’s disease and gut microbiota

Wang

Jin

2016

Sci. China Life Sci.

295

188

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Section: Microbial Infection and Admentioning

confidence: 99%

Alzheimer’s disease and gut microbiota

Wang

Jin

2016

Sci. China Life Sci.

295

188

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“…T. pallidum causes brain atrophy and Aβ deposition in the atrophic form of general paresis (68,69) and is a strong indication for involvement of spirochetes in AD pathogenesis.…”

Section: The Extrinsic Modelmentioning

confidence: 99%

“…Chronic diseases such as syphilis are frequently associated with deposition of amyloid (68,69). Amyloid is an integral component of spirochetes which may contribute to amyloid deposition in AD (70).…”

Section: The Extrinsic Modelmentioning

confidence: 99%

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Inflammasome Involvement in Alzheimer’s Disease

Olsen

Singhrao

2016

JAD

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Alzheimer's disease (AD) is a scourge of longevity that will drain enormous resources from public health budgets in the future. Currently, there is no diagnostic biomarker and/or treatment for this most common form of dementia in humans. AD can be of early familialonset or sporadic with a late-onset. Apart from the two main hallmarks, amyloid-beta and neurofibrillary tangles, inflammation is a characteristic feature of AD neuropathology.Inflammation may be caused by a local central nervous system insult and/or by peripheral infections. Numerous microorganisms are suspected in AD brains ranging from bacteria (mainly oral and non-oral Treponema species), viruses (Herpes simplex type I) and yeasts (Candida species). A causal relationship between periodontal pathogens/non-oral Treponema species of bacteria has been proposed via the amyloid-beta and inflammatory links.Periodontitis constitutes a peripheral oral infection that can provide the brain with intact bacteria and virulence factors and inflammatory mediators due to daily, transient bacteraemias. If and when genetic risk factors meet environmental risk factors in the brain, disease is expressed, in which neurocognition may be impacted, leading to the development of dementia. To achieve the goal of finding a diagnostic biomarker and possible prophylactic treatment for AD, there is an initial need to solve the etiological puzzle contributing to its pathogenesis. This review therefore addresses oral infection as the plausible aetiology of late onset AD (LOAD). ___________________________________________________________________________Keywords: Alzheimer's disease; pathogenesis; microorganisms; oral bacteria; direct cause 3 Alzheimer's disease (AD) is a neurodegenerative disease and the most common example of a group of diseases that manifest as dementia. It is associated with atrophy and specific neuronal death particularly in the hippocampal region of the brain (1). Research into AD pathogenesis, has flagged two main categories of the disease: the familial onset presentation accounts for around 2% of all AD cases and the sporadic form of late-onset AD also referred to as LOAD constitutes approximately 98% of the cases. LOAD displays genetic susceptibility traits of which the well-known risk factor is inheritance of the apolipoprotein (APOEɛ4) gene allele (2) and, appears to require an environmental factor for disease expression. For example a pathogen-host interaction can exacerbate neurocognition in some elderly individuals who if in their 80+ years likely become diagnosed with LOAD (3, 4). The rationale for this review therefore is to try to explain the aetiology in the vast proportion of LOAD cases that relies upon common risk factors. Several scientists have proposed, one of these to be peripheral infections (5-11), and the accompanying systemic and local inflammatory mediators (11)(12)(13). Of these, the plausible risk from oral infection is the main focus of this review. PREVALENCE OF ADAD is a burden of longevity resulting from the superior qualit...

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“…The surviving cells are able to expel strongly inflammatory components including LPSs [16]. The imputed role of pathogens in AD has been extensively reported for about over 200 different helical bacterial spirochete species [17], which may co-infect with other Gram-negative phylotypes [18][19][20][21][22][23][24][25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease

Andreadou

Pantazaki

Daniilidou

et al. 2017

JAD

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Abstract. Alzheimer's disease (AD) has been attributed to chronic bacterial infections. The recognition of human microbiota as a substantial contributor to health and disease is relatively recent and growing. During evolution, mammals live in a symbiotic state with myriads of microorganisms that survive at a diversity of tissue micro-surroundings. Microbes produce a plethora of secretory products [amyloids, lipopolysaccharides, virulence factors rhamnolipids (RLs), toxins, and a great number of neuroactive compounds]. The contribution of infectious microbial components to the pathophysiology of the human central nervous system including AD is considered potentially substantial, but the involvement of the RLs has never been reported. Here, RLs were isolated from serum and identified through various conventional methods including the colorimetric orcinol method, thin-layer chromatography, attenuated total reflection Fourier transform infrared (ATR-FTIR), and dot blot using antibodies against RLs. Dot blot demonstrated elevated RL levels in sera of AD patients compared to controls (p = 0.014). Moreover, ELISA showed similarly elevated RL levels in cerebrospinal fluid of both AD (0.188 versus 0.080) (p = 0.04) and mild cognitive impairment (0.188 versus 0.129) (p = 0.088) patients compared to healthy, and are wellcorrelated with the AD stages severity assessed using the Mini-Mental State Examination. These results provide conclusive evidence for the newly-reported implication of RLs in AD, adding it to the list of bacterial components, opening new avenues for AD investigation. Moreover, they strengthen and vindicate the divergence of research toward the exploration of bacterial involvement in AD generation and progression.

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Emerging roles of pathogens in Alzheimer disease

Cited by 170 publications

References 344 publications

Alzheimer’s disease and gut microbiota

Alzheimer’s disease and gut microbiota

Inflammasome Involvement in Alzheimer’s Disease

Rhamnolipids, Microbial Virulence Factors, in Alzheimer’s Disease

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