Biomarkers of neurodegenerative disorders: How good are they?

Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
Cell Research (Impact Factor: 12.41). 10/2004; 14(5):347-58. DOI: 10.1038/
Source: PubMed


Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies, biochemistries and genetics can give us comprehensive information regarding the nature of any particular disease. A good biomarker should be precise and reliable, distinguishable between normal and interested disease, and differential between different diseases. It is believed that biomarkers have great potential in predicting chances for diseases, aiding in early diagnosis, and setting standards for the development of new remedies to treat diseases. New technologies have enabled scientists to identify biomarkers of several different neurodegenerative diseases. The followings, for instance, are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated Beta-amyloid peptide for Alzheimer's disease (AD), Alpha-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson's disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington's gene mutations in Huntington's disease (HD). This article will focus on the most-recent findings of biomarkers belonging to the four mentioned neurodegenerative diseases.

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    • "DAT is also involved in the uptake of toxins generating Parkinson's syndrome. Thus, the localization of striatal, preferentially putamen DAT concentration is considered a high sensitivity parameter for the detection of early phases of PD and best molecular diagnostic marker (Marek et al., 2000; Rachakonda et al., 2004; Shinto et al., 2014). Discovery of Lewy bodies and Lewy neuritis, the characteristic lesions in brains of patients with PD and dementia is due to two mutations in α-synuclein gene. "
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    ABSTRACT: Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer’s and Parkinson’s disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis and Huntington’s disease, and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.
    Full-text · Article · Sep 2015
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    • "However, available memory tasks have not yet achieved sufficient diagnosis accuracy (i.e., combine sensitivity and specificity) as to grant them reliability in the detection of AD (Lowndes and Savage, 2007; Parra et al., 2010; Didic et al., 2011). Hence, there is a need for combined assessment tools which can improve the early diagnosis of dementia (Rachakonda et al., 2004; Dickerson et al., 2007; Dubois et al., 2007; Burns and Morris, 2008; Albert et al., 2011; Jack Jr. et al., 2011; Sperling et al., 2011). Event Related Potentials (ERPs), particularly the P300 wave, has proved to be sensitive to the early effects of AD (Muir et al., 1988; St Clair et al., 1988; Wright et al., 1988; Polich, 1989; Pokryszko-Dragan et al., 2003; Katada et al., 2004; Polich and Corey-Bloom, 2005; Ally et al., 2006; Bonanni et al., 2010; Lai et al., 2010). "
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    ABSTRACT: Only a small proportion of individuals with Mild Cognitive Impairment (MCI) will convert to dementia. Methods currently available to identify risk for conversion do not combine enough sensitivity and specificity, which is even more problematic in low-educated populations. Current guidelines suggest the use of combined markers for dementia to enhance the prediction accuracy of assessment methods. The present study adhered to this proposal and investigated the sensitivity and specificity of the electrophysiological component P300 and standard neuropsychological tests to assess patients with Alzheimer's disease (AD) and MCI recruited from a low-income country. The neuropsychological battery comprised tests of memory, attention, language, praxis, and executive functions. The P300 was recorded using a classical visual odd-ball paradigm. Three variables were found to achieve sensitivity and specificity values above 80% (Immediate and Delayed recall of word list - CERAD - and the latency of P300) for both MCI and AD. When they entered the model together (i.e., combined approach) the sensitivity for MCI increased to 96% and the specificity remained high (80%). Our preliminary findings suggest that the combined use of sensitive neuropsychological tasks and the analysis of the P300 may offer a very useful method for the preclinical assessment of AD, particularly in populations with low socioeconomic and educational levels. Our results provide a platform and justification to employ more resources to convert P300 and related parameters into a biological marker for AD.
    Full-text · Article · Dec 2012 · Frontiers in Neurology
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    • "Amyloid plaques are lesions consisting of compact deposit of amyloid peptides surrounded by reactive astrocytes , microglia, and dystrophic neuritis. Amyloidβ 1−42 (Aβ 1−42 ) and Aβ 1−40 are the main amyloid peptides that are found in the plaques which are produced by proteolytic cleavage of the amyloid-β protein precursor (AβPP) [1] [2] [3] [4]. Aβ 1−42 is the peptide that is deposited first in the process of AD and is the predominant form of Aβ in these plaques, whereas Aβ 1−40 is deposited later. "
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    ABSTRACT: The aggregation of amyloid-beta42 (Abeta42) constitutes one of the major pathogenic events in Alzheimer's disease (AD), and the study of regional cerebral blood flow (rCBF), using single photon emission computed tomography (SPECT), aids the diagnosis of AD. In this study, we evaluated whether there was a correlation between rCBF in brain regions and plasma levels of Abeta1-42 in AD. 29 patients (mean age 71 +/- 9) with a diagnosis of AD who fulfilled NINCDS-ADRDA criteria with a mean Mini-Mental Status Examination score of 15 +/- 9 and 16 normal controls (mean age 64 +/- 8) underwent SPECT brain imaging with hexamethylpropylene amine oxime, and semiquantitative analysis of rCBF was performed. Plasma samples were collected the same day of the SPECT and plasma Abeta1-42 measured by ELISA. A significant reduction of rCBF was observed in most regions in AD compared to controls, whereas mean plasma Abeta42 did not differ between the two groups. There was no correlation between rCBF in any region and plasma Abeta42 nor any correlations between gender, age, and severity with plasma levels of Abeta42. Since rCBF is coupled to neuronal activity, we conclude that plasma Abeta1-42 concentration is independent of neuronal function in every single region of the brain.
    Full-text · Article · Mar 2009 · Journal of Alzheimer's disease: JAD
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