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ESTUDIO DE MARCADORES BIOLOGICOS EN LA ENFERMEDAD DE ALZHEIMER

Electronic Journal of Biomedicine 01/2006;
Source: DOAJ

ABSTRACT SUMMARY: STUDY OF BIOCHEMICAL MARKERS OF ALZHEIMER'S DISEASE.Alzheimer´ disease (AD) affects in the World up to 25 million people and it is the most common form of dementia among older people in the Western countries. The disease usually begins after age 60, and risk goes up with age. AD can be classified as of early beginning, if it appears before the 60-65 years and of late beginning, if it appears later.In this report, the main biological parameters in Alzheimer´disease are studied to try to differentiate it from other degenerative diseases, since its early diagnosis is of great importance.The gene Apo E is located in the human chromosome 19 and it contains 4 exons that codes for the 299-amino acid protein named Apolipoprotein (apo) E, that is genetically polymorphic. There are three common codominant alleles, designated E2 (with a protective effect against AD), E3 (the more prevalent isoform) and E4 (which constitutes a major risk factor for AD) whose genetic basis lies within codons 112 and 158 of the gene. The three common apo E alleles lead to six common phenotypes, three homozigotes (apo E2/2, E3/3 and E4/4) and three heterozigotes (apo E3/2, E4/3 and E4/2), all originally disclosed by isoelectric focusing and immunoblotting.As the tau it is a protein intracelular, low CSF levels can be expected. Nevertheless and by the reasons given in above paragraph, tau levels were increased in AD patients in comparison with healthy controls, especially in those having one or two Apo E4 alleles. Therefore, the test based on the quantitative determination of tau proteins in the CSF is of great help in the diagnosis of AD.At the present time, phospho-tau is the best marker. However, it is not sensitive and specific enough to detect all the cases of AD. Therefore, the combination of Ab-42, phospho-tau and tau levels in CSF can be used as a help to confirm or exclude AD. RESUMEN:La enfermedad de Alzheimer afecta en el mundo a unas 25 millones de personas, siendo la causa mas frecuente de demencia en los paises occidentales. Su prevalencia va en aumento, debido al envejecimiento de la población. Por la edad de aparición la EA se puede clasificar en presenil ó de inicio temprano si aparece antes de los 60-65 años y senil o de inicio tardio si aparece después.En esta revisión se estudian los principales parámetros biológicos a utilizar en la enfermedad de Alzheimer e intentar diferenciarla de otras patologías degenerativas, ya que el diagnostico precoz de la EA es de gran importancia.El gen Apo E esta localizado en el cromosoma humano 19 y contiene 4 exones que codifica la apolipoproteina E de 299 aminoácidos. Las tres isoenzimas de la Apo E son la Apo E2, E3 y E4 y son productos de los tres alelos de cada locus génico. Tres fenotipos homozigoticos (apo E2/2, E3/3 y E4/4) y tres heterizigóticos (apo E3/2, E4/3 y E4/2) resultan de la expresión de cada uno de los tres alelos. La sustitución de los aminoácidos en los codones 112 y 158 conllevan a las diferencias entre apo E2, E3 y E4.Como la tau se trata de una proteína intracelular el nivel hallado en LCR es bajo. El desarrollo de una elevada afinidad por los anticuerpos monoclonales altamente específicos para la tau ha conducido al desarrollo de test para la detección de la tau en LCR y un número elevado de pacientes con Alhzeimer y controles han mostrado una elevada expresión de la tau en las células neuronales afectadas. Además los test basados en la determinación cuantitativa de la proteína tau en el LCR puede ser de gran ayuda en el diagnóstico de la EA.En la actualidad, el marcador en LCR que muestra mayor especificidad es fosfo-tau. No obstante la determinación conjunta de los tres marcadores tau, fosfo-tau y AB42 en LCR, aumenta la especificidad y sensibilidad respecto a su utilización individual.

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