Reduced KIAA0471 mRNA expression in Alzheimer's patients: A new candidate gene product linked to the disease?

Abstract

Alzheimer's disease (AD) phenotype complexity raises the question whether genetic features remain unknown. Although a few percentage of patients are familial cases linked to mutations in amyloid precursor protein, presenilin 1 or presenilin 2 genes, the remainder are considered mainly sporadic late-onset cases with a complex etiology. However, changes in gene expression or other genetic features of the individual can clearly contribute to develop the illness. Consequently, in this paper we have focused on the identification of new genes, the expression of which is altered in AD. We used the technique of differential display reverse transcriptase-polymerase chain reaction (DDRT-PCR) in order to study the gene expression differences in brain tissue from patients in an advanced stage of AD. After studying medial septum and hippocampus brain areas, we found an inhibition of the KIAA0471 gene expression in three out of six AD patients, including one with a presenilin 1 gene mutation. This gene encodes for a large protein that presents, in its predicted form, 95% homology with IDN4-GGTR sequences. These results may provide significant clues for understanding the molecular mechanisms underlying septohippocampal neurodegeneration. In addition, they may open a new area of research for diagnostic and therapeutic tools, the relevance of which is also considered. © Oxford University Press 2004; all rights reserved.