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Biological Markers in Alzheimer's Disease

Published online by Cambridge University Press:  02 December 2014

Peter Bailey
Peter Bailey*
Affiliation:
Department of Medicine, Dalhousie University, Saint John Regional Hospital, Saint John, New Brunswick, Canada
*
Department of Medicine, Dalhousie University, Saint John Regional Hospital, Suite 5DN - 400 University Avenue, P.O. Box 2100, Saint John, New Brunswick, E2L 4L2, Canada.
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Abstract

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Biomarkers are required to improve our diagnostic sensitivity and specificity and to monitor the biological activity of the Alzheimer’s disease (AD) in terms of the burden of neural involvement and the tempo of disease progression. Biomarkers will initially supplement our more traditional neuropsychological and imaging markers but may eventually evolve into useful surrogate endpoints in AD research. These markers may also provide important mechanistic clues to the pharmacological action of anti-dementia compounds. At this point, the combination of elevated cerebrospinal fluid phosphorylated TAU (CSF p-TAU) proteins and low CSF A²1-42 are the only biomarkers with the sensitivity and specificity to serve as useful diagnostic biomarkers capable of distinguishing AD from other dementias in the early stages. Advances in non CSF tests is urgently required. Markers assessing the progression of disease do not necessarily require the same high disease specificity as diagnostic markers, but need to be sensitive to changes in disease state. At present, candidate markers fall under four main biological rationales: 1. Specific markers of AD neuropathology; 2. Non-specific markers of neural degeneration; 3. Markers of oxidative stress; 4. Markers of neural inflammation. It is foreseeable that a panel of such markers might prove advantageous. It will be important to develop “non-invasive “ markers utilizing readily obtainable tissue samples such as serum or urine to monitor disease progression (or hopefully regression). Repeated sampling would allow for comparison with traditional neuropsychological and imaging measures. The assays themselves will need to be reproducible, reliable and relatively inexpensive. Unfortunately, these biomarkers are in the formative stages of testing and results at present are inconclusive. To facilitate biomarker development in the future it would be highly advantageous to begin to collect and store biological specimens as an adjunct to current research in AD.

Résumé:

RÉSUMÉ:

Nous avons besoin de biomarqueurs pour améliorer la sensibilité et la spécificité du diagnostic et pour suivre l'activité biologique de la maladie d'Alzheimer (MA) en ce qui concerne le fardeau de l'atteinte neurologique et le rythme de progression de la maladie. Au début, les biomarqueurs serviront de supplément aux marqueurs traditionnels de neuropsychologie et d'imagerie, mais éventuellement ils pourraient devenir des critères d'évaluation de substitution dans la recherche sur la MA. Ces marqueurs pourraient également fournir des indices concernant les mécanismes d'action pharmacologique des médicaments anti-démence. Actuellement, la combinaison d'un taux élevé de protéines phosphorylées TAU dans le liquide céphalorachidien (LCR) et d'un taux bas d'Abl-42 dans le LCR sont les seuls biomarqueurs qui ont une sensibilité et une spécificité permettant de les utiliser comme biomarqueurs diagnostiques capables de distinguer la MA des autres démences aux stades précoces. Il est urgent de développer des tests autres que les tests sur le LCR. Les marqueurs pour évaluer la progression de la maladie ne doivent pas nécessairement posséder une spécificité aussi élevée que les marqueurs diagnostiques, mais ils doivent être sensibles au changement au cours de la maladie. Actuellement, les marqueurs candidats se classent en quatre groupes principaux au point de vue biologique : 1. Des marqueurs spécifiques de la neuropathologie de la MA; 2. Des marqueurs non spécifiques de la dégénérescence neuronale; 3. Des marqueurs du stress oxydatif; 4. Des marqueurs de l'inflammation neuronale. Il est probable qu'une batterie de ces marqueurs pourra s'avérer utile. Il sera important de développer des marqueurs non effractifs utilisant des échantillons de tissus faciles à obtenir, comme du sérum ou de l'urine, pour surveiller la progression de la maladie ou même sa régression. Un échantillonnage sérié permettrait de les comparer aux mesures traditionnelles de neuropsychologie ou d'imagerie. Les analyses devront être reproductibles, fiables et relativement peu coûteuses. Malheureusement, ces biomarqueurs sont encore en évaluation et les résultats sont non concluants. Il serait très avantageux de commencer à récolter et à conserver des spécimens biologiques dans le cadre de la recherche actuelle sur la MA pour faciliter le développement de biomarqueurs dans l'avenir.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 34 , Issue S1 , March 2007 , pp. S72 - S76
Copyright
Copyright © The Canadian Journal of Neurological 2007

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