Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease

Watabe-Rudolph, Masami; Song, Zhangfa; Lausser, Ludwig; Schnack, Cathrin; Begus‐Nahrmann, Yvonne; Scheithauer, Marcel; Rettinger, Gerhard; Otto, Markus; Tumani, Hayrettin; Thal, Dietmar Rudolf; Attems, Johannes; Jellinger, K. A.; Kestler, Hans A.; Arnim, Christiane A.F. von; Rudolph, K. Lenhard

doi:10.1212/wnl.0b013e318247caa1

Cited by 102 publications

(70 citation statements)

References 43 publications

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“…During persistence it may release toxic products continuously and induce pro-inflammatory cytokines at low levels which become an additional burden to a host already challenged by age, poor diet, restricted exercise as well as any genetic susceptibilities. Itzaki and Wozniak (10) proposed as a powerful biomarker of AD (146). In AD brains, cytoplasmic material in a small number of cells was targeted by antibodies with immunoreactivity to yeast cells (147).…”

Section: Hsv-1 Is a Strong Risk Factor For Ad In The Brains Of Those mentioning

confidence: 99%

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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Section: Hsv-1 Is a Strong Risk Factor For Ad In The Brains Of Those mentioning

confidence: 99%

Inflammasome Involvement in Alzheimer’s Disease

Olsen

Singhrao

2016

JAD

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“…NAG has previously been identified as a secreted marker of DNA damage that is upregulated prior to onset of cellular senescence and that associates with human aging and the evolution of age associated disease, such as Alzheimers' disease [8,11,12]. Here, we report a study of the levels in plasma of patients with gastro-intestinal adenocarcinoma.…”

Section: Discussionmentioning

confidence: 87%

Plasma N -acetyl-glucosaminidase in advanced gastro-intestinal adenocarcinoma correlates with age, stage and outcome

et al. 2014

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Background: N-acetyl-glucosaminidase (NAG) is a potential marker of genotoxicity. We retrospectively analyzed plasma NAG and clinico-pathologic features in advanced gastrointestinal adenocarcinoma patients. Methods: Plasma from 118 patients and 51 healthy volunteers was analyzed for associations between NAG levels and age, disease presence, stage, treatment responses and survival. Results: Pretreatment NAG correlated with age but was independently increased in metastatic versus locally advanced disease, particularly in gastric/esophageal patients. NAG was also associated with reduced overall survival. In subgroup analysis, increased NAG activity between day 1 and 2 of chemotherapy cycle 1 correlated with treatment response. Conclusion: We demonstrated that NAG correlates with gastrointestinal cancer outcomes. Further studies are required to determine if plasma markers of genotoxicity can be useful for disease monitoring. BackgroundBiological age is a risk factor in many cancers and the molecular factors underpinning cellular aging including telomere dysfunction and DNA damage responses have been shown to be common features at early stages of carcinogenesis [1]. These molecular events have been investigated in tumor samples by approaches including fluorescence hybridization and immunohistochemistry [2][3][4] and are intrinsically involved in cell aging and cellular senescence, correlating with tumor initiation of gastrointestinal tumors, such as adenocarcinoma of the stomach and colon [5]. There is considerable current interest in clinical application of markers of cellular senescence in cancer [6,7]. However, the 'senectome' is poorly defined and therefore there is a need to define the most appropriate markers for use in different settings. Furthermore, in clinical practice, there is a need for markers that are easy to measure in patient material and that are accessible to repeat sampling, ideally in blood for treatment monitoring.Recently, we described the identification of secreted proteins including the Chitinase enzyme N-acetyl-glucosaminidase (NAG) that are elevated in aging human fibroblasts preceding the onset of senescence and in response to DNA damage. NAG can be detected in human blood and increases with

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“…In conclusion, the discrimination between ALS and other syndromes that mimic ALS is difficult. Thus, comparative investigations at molecular level in ALS and other neurodegenerative diseases [97,98,99] are necessary in order to identify specific biomarkers for a correct diagnosis. In this regard, clarification might come from the recent identification of new genes or pathways that could be used as ‘fingerprints' for ALS or ALS risk factors [100,101,102,103].…”

Section: Discussionmentioning

confidence: 99%

The Big Bluff of Amyotrophic Lateral Sclerosis Diagnosis: The Role of Neurodegenerative Disease Mimics

et al. 2015

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Neurodegenerative diseases include a significant number of pathologies affecting the nervous system. Generally, the primary cause of each disease is specific; however, recently, it was shown that they may be correlated at molecular level. This aspect, together with the exhibition of similar symptoms, renders the diagnosis of these disorders difficult. Amyotrophic lateral sclerosis is one of these pathologies. Herein, we report several cases of amyotrophic lateral sclerosis misdiagnosed as a consequence of features that are common to several neurodegenerative diseases, such as Parkinson's, Huntington's and Alzheimer's disease, spinal muscular atrophy, progressive bulbar palsy, spastic paraplegia and frontotemporal dementia, and mostly with the lysosomal storage disorder GM2 gangliosidosis. Overall reports highlight that the differential diagnosis for amyotrophic lateral sclerosis should include correlated mechanisms.

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Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease

Abstract: Taken together, the findings in this study provide experimental evidence that DNA damage markers are significantly increased in AD and non-AD dementia. The biomarkers identified outperformed the standard CSF markers for diagnosing AD and non-AD dementia in the cohort investigated.

Cited by 102 publications

References 43 publications

Inflammasome Involvement in Alzheimer’s Disease

Inflammasome Involvement in Alzheimer’s Disease

Plasma N -acetyl-glucosaminidase in advanced gastro-intestinal adenocarcinoma correlates with age, stage and outcome

The Big Bluff of Amyotrophic Lateral Sclerosis Diagnosis: The Role of Neurodegenerative Disease Mimics

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