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Biomarker in Cerebrospinal Fluid Detects Alzheimer's Disease

By LabMedica International staff writers
Posted on 28 Dec 2010
The total levels of certain proteins in cerebrospinal fluid (CSF) can be related to gene variation and associated with Alzheimer's disease (AD).

A genomic-wide analysis of CSF searched for biomarkers that would help physicians make an early diagnosis of AD, and specifically for genetic variations that could be related to CSF levels of three proteins. The main effect of single nucleotide polymorphisms (SNPs) under an additive genetic model was assessed on each of five CSF biomarkers.

In a US national collaborative study, carried out at Indiana University, (Indianapolis, IN, USA), scientists analyzed a total of 374 non-Hispanic Caucasian participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort that included quality-controlled CSF and genotype data. In this genome-wide association study, they looked for genetic variations that could be related to CSF levels of the three proteins, beta amyloid, tau and phosphorylated tau, all of which are linked to damage seen in brains of Alzheimer's patients.

The primary novel finding was that a gene known as enhancer of polycomb homolog 2 (EPC2) was associated with total levels of the tau protein in the cerebrospinal fluid. This gene, which has not previously surfaced in other studies looking for Alzheimer-related markers, has been associated with a gene deletion syndrome that includes mental retardation, short stature, and epilepsy. EPC2 is also involved in the formation of a DNA structure, heterochromatin that plays a role in the activation and control of gene activity. That process, called epigenetics, refers to the alteration of gene expression by factors beyond the instructions in the DNA itself, including environmental factors.

Andrew J. Saykin, Psy.D., who leads the ADNI genetics component, said, "The association of CSF tau and the EPC2 gene suggests a possible epigenetic mechanism that warrants follow-up in other samples. These epigenetic processes, in which genome function can be modified through interacting with the internal or external environment, are suspected of playing a role in neurodegenerative diseases such as Alzheimer's." The study was published online on December 1, 2010, in Neurology.

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