TNF-α and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects

Kamer, Angela R.; Craig, Ronald G.; Pirraglia, Elizabeth; Dasanayake, Ananda P.; Norman, Robert G.; Boylan, Robert; Nehorayoff, Andrea; Glodzik, Lidia; Bryś, Mirosław; Leon, Mony J. de

doi:10.1016/j.jneuroim.2009.08.013

Cited by 229 publications

(234 citation statements)

References 54 publications

(77 reference statements)

Supporting

Mentioning

222

Contrasting

Unclassified

Order By: Relevance

“…This study supports the literature on elevated antibodies to periodontal diseaseassociated bacteria such as P. gingivalis, being found in AD patients (7). Furthermore, in 2,355 people 60 years and over, the third NHANES study found associations between periodontitis and cognitive impairment and between measures of immunoglobulin to P. gingivalis and cognitive test performance (96,97).…”

Section: Periodontal Bacterial Pathogens Are Related To Adsupporting

confidence: 89%

“…The cells from this region of the brain are fully equipped with the CD14 receptor and the toll-like receptor 4 (TLR 4) to recognize LPS from the peripheral blood circulation (27,28). Hence, elements of systemic infections such as those 8 originating from Gram-negative, highly virulent oral pathogens, bronchopneumonia and urinary tract infections (3,4,7,57,58) The same researchers subsequently demonstrated that astroglia, microglia, neurons, endothelial cells and monocytes in the LOAD brain are permissive to this bacterium. The mechanisms of pathogenesis differ between actively-and persistently-infecting chlamydiae and it is in the persistent state that these organisms cause chronic disease (64, 65).…”

mentioning

confidence: 99%

“…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)(6)(7)(8)(9)(10)(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.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Inflammasome Involvement in Alzheimer’s Disease

Olsen

Singhrao

2016

JAD

View full text Add to dashboard Cite

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...

show abstract

Section: Periodontal Bacterial Pathogens Are Related To Adsupporting

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Inflammasome Involvement in Alzheimer’s Disease

Olsen

Singhrao

2016

JAD

View full text Add to dashboard Cite

show abstract

“…In addition, PET imaging studies revealed that cognitive status in patients with AD is inversely correlated with microglial activation, but not Aβ load. 52,53 Finally, in accordance with the above mentioned genome-wide association studies, 7,8 chronic inflammatory diseases and conditions in humans, including atherosclerosis, obesity, diabetes, depression, and periodontitis, [54][55][56][57][58][59][60] all represent either risk factors for or correlate strongly with the risk of late-onset AD.…”

Section: Inflammation-a Key Playermentioning

confidence: 98%

Deciphering the mechanism underlying late-onset Alzheimer disease

2012

View full text Add to dashboard Cite

Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-(A) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between A and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence of A accumulation in late-onset AD. Abstract | Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-β (Aβ) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between Aβ and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence ...

show abstract

“…It was shown that periodontal treatment may lead to favorable systemic CRP levels (43,45). The possible relationships with Alzheimer's disease (AD), which is a neurodegenerative disease, and periodontal diseases, have also been investigated (46,47,48). When compared to the healthy individuals, people with AD had elevated plasma Ig G and TNF-α levels against periodontal bacteria (P. gingivalis, T. forsythia ve A. actinomycetemcomitans), There were no differences found in IL-1β and IL-6 levels (46).…”

Section: Periodontal Statusmentioning

confidence: 99%

Multiple Sclerosis and Dentistry: A Contemporary Evaluation

Hatipoğlu¹,

Kabay²,

Hatipoğlu³

2015

tnd

View full text Add to dashboard Cite

Multipl skleroz (MS) santral sinir sistemini etkileyen kronik, enflamatuvar, demiyalizan bir hastalıktır. Hastalık otoimmün özellikler sergilemektedir. Etiyolojisi tam olarak bilinmemesine rağmen çevresel ve genetik faktörler suçlanmaktadır. MS ile diş hekimliği uygulama ve klinik tablolarının arasındaki ilişki literatürde sıklıkla tartışılmıştır. Gerek MS teşhisi, gerekse de dental tedavinin gerçekleştirilmesinde özel dikkat gerektiren süreçlerin bulunması MS hastalarının genel ve dental sağlık durumlarının optimize edilmesi için disiplinler arası işbirliğini zorunlu kılmaktadır. Bu derlemede, MS ile diş hekimliği alanında yapılan çalışmalar, MS'i bulunan bireylerde dental tedavi sürecindeki öneriler irdelenmiş ve tartışılmıştır. ( ÖzetMultiple sclerosis (MS) is an inflammatory, demyelinating condition affecting the central nervous system. MS exhibits characteristics of an auto-immune disease. Etiology of this condition remains unknown but environmental and genetic factors are often thought to be responsible. A possible relationship between dentistry and MS has often been mentioned in the literature. Special attention and interdisciplinary cooperation are required in the diagnosis of MS and the application of dental treatments in order to optimize general and dental health status of patients with MS. In this review, MS-dental related studies and recommendations for dental treatment approaches for individuals with MS are discussed.

show abstract

TNF-α and antibodies to periodontal bacteria discriminate between Alzheimer's disease patients and normal subjects

Cited by 229 publications

References 54 publications

Inflammasome Involvement in Alzheimer’s Disease

Inflammasome Involvement in Alzheimer’s Disease

Deciphering the mechanism underlying late-onset Alzheimer disease

Multiple Sclerosis and Dentistry: A Contemporary Evaluation

Contact Info

Product

Resources

About