The Use of Biomarkers in the Elderly: Current and Future Challenges

Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
Biological Psychiatry (Impact Factor: 10.26). 09/2005; 58(4):272-6. DOI: 10.1016/j.biopsych.2005.05.016
Source: PubMed


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 [9]. In the review [9], 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. "
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    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 · 1.56 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. "
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    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 · 2.58 Impact Factor
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    • "One of the criteria for an ideal diagnostic biomarker for AD is validation against autopsy-proven cases [4]. However, Ranganathan et al. [45] report big differences between the protein profile of CSF from live patients with amyotrophic lateral sclerosis (ALS) and that of post-mortem brain tissues. "
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    ABSTRACT: The field of proteomics has made leaps and bounds in the last 10 years particularly in the fields of oncology and cardiovascular medicine. In comparison, neuroproteomics is still playing catch up mainly due to the relative complexity of neurological disorders. Schizophrenia is one such disorder, believed to be the results of multiple factors both genetic and environmental. Affecting over 2 million people in the US alone, it has become a major clinical and public health concern worldwide. This paper gives an update of schizophrenia biomarker research as reviewed by Lakhan in 2006 and gives us a rundown of the progress made during the last two years. Several studies demonstrate the potential of cerebrospinal fluid as a source of neuro-specific biomarkers. Genetic association studies are making headway in identifying candidate genes for schizophrenia. In addition, metabonomics, bioinformatics, and neuroimaging techniques are aiming to complete the picture by filling in knowledge gaps. International cooperation in the form of genomics and protein databases and brain banks is facilitating research efforts. While none of the recent developments described here in qualifies as biomarker discovery, many are likely to be stepping stones towards that goal.
    Behavioral and Brain Functions 02/2009; 5(1):2. DOI:10.1186/1744-9081-5-2 · 1.97 Impact Factor
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