The use of biomarkers in the elderly: current and future challenges.
ABSTRACT Biomarkers are hypothesized but not frequently used in research with the elderly because of a general paucity of supportive scientific data. However, there is an obvious need for greater diagnostic specificity and sensitivity across many diagnoses in the elderly, as well as good targets for therapeutic trials. The authors reviewed the available information in this field as part of a general review of geriatric research for the . Potential biomarkers with pathophysiologic significance have been studied in the field of Alzheimer disease research with some success, especially in the area of genetic markers (apolipoprotein E [APOE] epsilon4 allele), neuroimaging, and cerebrospinal fluid markers (beta-amyloid and tau). While some progress has been made in the search for adequate biomarkers in the elderly, in particular with Alzheimer disease, much more work is needed before these potential biomarkers can be reliably used in clinical practice.
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- "However, when one considers the characteristics of an ideal biomarker as outlined for use in Alzheimer's disease, the main concerns are that the test measures an underlying component of the disease, is valid and specific, and would be easily and reliably measured across laboratories . In the review , the authors point out that valuable biomarkers could be either " trait " dependant (ApoE4 genotype ) or " state " dependant (CSF í µí»½-amyloid level). It may be that some individuals support the notion that an optimal biomarker needs to be consistent with an invariant diagnostic label, in a similar way that, the term " endophenotype " may be used to indicate an " intermediate " step involved in risk for schizophrenia, as being stable over time in order to aid identification of associated genes. "
ABSTRACT: Biomarkers have been sought after in the field of schizophrenia research for decades. In this paper, we discuss some of the concepts around developing biomarkers in an effort to understand why the use of biomarkers for schizophrenia has not been realized. In particular, we address the following 4 questions. Why would we need a diagnostic biomarker for schizophrenia? How is a biomarker typically defined and how does that influence the discovery of biomarkers in schizophrenia? What is the best use of biomarkers in schizophrenia? Do any biomarkers for schizophrenia currently exist? Thus, while we suggest that no biomarker currently exists for schizophrenia, the heterogeneity associated with schizophrenia will most likely need to be taken into account which will result in multiple biomarkers that identify the multiple underlying pathophysiological processes involved in schizophrenia. Therefore, much additional work will be required prior to obtaining any well-established biomarkers for schizophrenia.Disease markers 07/2013; 35(1):3-9. DOI:10.1155/2013/510402 · 2.17 Impact Factor
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- "Several studies have been conducted to identify cerebrospinal fluid (CSF) and blood biomarkers for AD, and the only reliable markers found were a decrease in amyloid-beta 42 (A␤42) and increase in total tau and phosphorylated tau (Blennow and Hampel, 2003; Sunderland et al., 2005). These CSF markers such as high total tau, high phosphor-tau and low A␤42 (Buerger et al., 2002; Hansson et al., 2006; Sunderland et al., 2003), however, are not optimal biomarkers since the lumbar puncture method must be used to obtain CSF, which is an invasive procedure that causes pain. "
ABSTRACT: The neurofibrillary tangles (NFTs) formed by the accumulation of abnormal tau filaments have been shown to be involved in Alzheimer's disease (AD) brain degeneration. In this study, a tau transgenic mouse (pNSE/htau23) model was used to monitor changes in protein levels and to search for novel biomarker candidates suitable for the early diagnosis of AD before onset of clinical symptoms. Plasma samples from 2-month (n=13, asymptomatic) and 4-month (n=7, symptomatic) tau transgenic mice were compared to the control group (n=8) by 2-dimensional gel electrophoresis (2-DE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three proteins, ATP synthase, Adenosine kinase and Regucalcin showed significantly decreased levels in the plasma of tau transgenic mouse, which was further confirmed by Western blotting. This study suggests that these proteins could be used as candidate biomarkers for early diagnosis of AD in combination with previously discovered protein biomarkers.International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 03/2012; 30(4):277-83. DOI:10.1016/j.ijdevneu.2012.01.011 · 2.92 Impact Factor
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- "A. Hye et al. found for Alzheimer's disease—most studies have searched for such markers in CSF, as it is more likely to reflect the metabolic state of brain (Sunderland et al., 2005). However, plasma markers might exist if either plasma characteristics change in response to brain disease or if Alzheimer's disease has a systemic metabolic state that is reflected in the periphery. "
ABSTRACT: Alzheimer's disease is a common and devastating disease for which there is no readily available biomarker to aid diagnosis or to monitor disease progression. Biomarkers have been sought in CSF but no previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry to seek biomarkers in peripheral tissue. We performed a case-control study of plasma using this proteomics approach to identify proteins that differ in the disease state relative to aged controls. For discovery-phase proteomics analysis, 50 people with Alzheimer's dementia were recruited through secondary services and 50 normal elderly controls through primary care. For validation purposes a total of 511 subjects with Alzheimer's disease and other neurodegenerative diseases and normal elderly controls were examined. Image analysis of the protein distribution of the gels alone identifies disease cases with 56% sensitivity and 80% specificity. Mass spectrometric analysis of the changes observed in two-dimensional electrophoresis identified a number of proteins previously implicated in the disease pathology, including complement factor H (CFH) precursor and alpha-2-macroglobulin (alpha-2M). Using semi-quantitative immunoblotting, the elevation of CFH and alpha-2M was shown to be specific for Alzheimer's disease and to correlate with disease severity although alternative assays would be necessary to improve sensitivity and specificity. These findings suggest that blood may be a rich source for biomarkers of Alzheimer's disease and that CFH, together with other proteins such as alpha-2M may be a specific markers of this illness.Brain 12/2006; 129(Pt 11):3042-50. DOI:10.1093/brain/awl279 · 10.23 Impact Factor