Sialic acid, homocysteine and CRP: Potential markers for dementia

Davis, Gershwin; Baboolal, Nelleen; Nayak, Shivanand; McRae, Amanda

doi:10.1016/j.neulet.2009.09.035

Cited by 29 publications

(19 citation statements)

References 29 publications

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“…Its reliability has several limitations as human CRP levels greatly vary, depending on ethnicity, gender, and genetics, and it has also been associated with obesity and weight loss 64,65. In addition, it has been described as an indicator/ marker for non-cardiac related pathologies such as anastomotic leakage, systemic lupus erythematosus (SLE), and dementia 66–68…”

Section: Clinically Relevant Cardiac Markersmentioning

confidence: 99%

Novel Cardiac-Specific Biomarkers and the Cardiovascular Continuum

2012

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The concept of the cardiovascular continuum, introduced during the early 1990s, created a holistic view of the chain of events connecting cardiovascular-related risk factors with the progressive development of pathological-related tissue remodelling and ultimately, heart failure and death. Understanding of the tissue-specific changes, and new technologies developed over the last 25–30 years, enabled tissue remodelling events to be monitored in vivo and cardiovascular disease to be diagnosed more reliably than before. The tangible product of this evolution was the introduction of a number of biochemical markers such as troponin I and T, which are now commonly used in clinics to measure myocardial damage. However, biomarkers that can detect specific earlier stages of the cardiovascular continuum have yet to be generated and utilised. The majority of the existing markers are useful only in the end stages of the disease where few successful intervention options exist. Since a large number of patients experience a transient underlying developing pathology long before the signs or symptoms of cardiovascular disease become apparent, the requirement for new markers that can describe the early tissue-specific, matrix remodelling process which ultimately leads to disease is evident. This review highlights the importance of relating cardiac biochemical markers with specific time points along the cardiovascular continuum, especially during the early transient phase of pathology progression where none of the existing markers aid diagnosis.

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Section: Clinically Relevant Cardiac Markersmentioning

confidence: 99%

Novel Cardiac-Specific Biomarkers and the Cardiovascular Continuum

2012

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“…All these studies used gel based proteomics as the discovery tool and the fact that textual analysis identifies the same proteins before these proteomic studies were performed is a strong indicator of the power of the method. Other promising candidates suggested by textual analysis, and where there is published data suggesting that these proteins are altered either in blood or CSF, include CRP [17-19], Complement factor 1 [20,21], butyrylcholinesterase [22] and BACE1 [23,24]. In all but the case of butyrylcholinesterase, this biomarker data was published after the IN lock-down and hence these biomarker utility data are independent of the IN and act as independent proof of concept.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer's disease biomarker discovery using in silico literature mining and clinical validation

et al. 2012

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BackgroundAlzheimer’s Disease (AD) is the most widespread form of dementia in the elderly but despite progress made in recent years towards a mechanistic understanding, there is still an urgent need for disease modification therapy and for early diagnostic tests. Substantial international efforts are being made to discover and validate biomarkers for AD using candidate analytes and various data-driven 'omics' approaches. Cerebrospinal fluid is in many ways the tissue of choice for biomarkers of brain disease but is limited by patient and clinician acceptability, and increasing attention is being paid to the search for blood-based biomarkers. The aim of this study was to use a novel in silico approach to discover a set of candidate biomarkers for AD.MethodsWe used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of assertional metadata derived from relevant legacy information. We then assessed the validity of this approach using direct assays of the identified biomarkers in plasma by immunodetection methods.ResultsUsing this in silico approach, we identified 25 biomarker candidates, at least three of which have subsequently been reported to be altered in blood or CSF from AD patients. Two further candidate biomarkers, indicated from the in silico approach, were choline acetyltransferase and urokinase-type plasminogen activator receptor. Using immunodetection, we showed that, in a large sample set, these markers are either altered in disease or correlate with MRI markers of atrophy.ConclusionsThese data support as a proof of concept the use of data mining and in silico analyses to derive valid biomarker candidates for AD and, by extension, for other disorders.

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“…Although it is known that Hcy caused cerebral vascular dementia (Nilsson et al ., 2008; Davis et al ., 2009; Kivipelto et al ., 2009; Regalado Dona et al, 2009), it was unclear whether it led to decrease in vascular density and vasospasm. We demonstrated the HHcy caused decrease in vascular density in the brain (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…The elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) cause vascular dementia, cerebral vascular complication and retardation (Nilsson et al ., 2008; Sala et al ., 2008; Davis et al ., 2009; Kivipelto et al ., 2009; Regalado Dona et al, 2009). Hyperhomocysteinemia causes constrictive vascular remodelling by increased collagen deposition in the vessel wall (Guo et al ., 2008).…”

Section: Introductionmentioning

confidence: 99%

X-ray imaging of differential vascular density in MMP-9−/−, PAR-1−/+, hyperhomocysteinemic (CBS−/+) and diabetic (Ins2−/+) mice

Givvimani

Sen

Tyagi

et al. 2010

Archives of Physiology and Biochemistry

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Although protease activated receptor-1 (PAR-1) and matrix metalloproteinase-9 (MMP-9) play significant role in vascular remodelling in hyperhomocysteinemia (HHcy due to cystathionine beta synthase deficiency, CBS−/+) and diabetes, mechanism remains nebulous. We hypothesized that differential vascular density and remodelling in different vascular beds in HHcy and diabetes were responsible for an adaptive metabolic homeostasis during the pathogenesis. To test this hypothesis, vascular density in mice lacking PAR-1, MMP-9, CBS and Insulin-2 gene mutant (Ins2−/+, Akita) was measured and compared with wild type (WT, C57BL/6J) mice. The vascular density was detected by x-ray angiography using KODAK 4000 MM image station, using barium sulphate as contrasting agent. The % vascular density in the hearts of WT, CBS−/+ (HHcy), MMP-9−/−, PAR-1−/+ and Ins2−/+ (type-1 diabetes) was 100 ± 2.8, 85 ± 3.3, 90 ± 3.3, 95 ± 3.8 and 73 ± 1.7, respectively. The vascular density in CBS−/+ and Akita hearts decreased while it was increased in lungs of CBS−/+ and MMP-9−/−. There was decreased vascular density in liver and kidney of Akita mice. Vascular density in brain, kidney and mesentery was decreased in CBS−/+ mice. These findings support the notation that metabolic derangement in diabetes and HHcy causes the chronic decline and/or rarefaction in vascular density.

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Sialic acid, homocysteine and CRP: Potential markers for dementia

Cited by 29 publications

References 29 publications

Novel Cardiac-Specific Biomarkers and the Cardiovascular Continuum

Novel Cardiac-Specific Biomarkers and the Cardiovascular Continuum

Alzheimer's disease biomarker discovery using in silico literature mining and clinical validation

X-ray imaging of differential vascular density in MMP-9−/−, PAR-1−/+, hyperhomocysteinemic (CBS−/+) and diabetic (Ins2−/+) mice

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