title: 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.
authors.affiliation: Unitat de Bioquímica, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Facultat de Medicina, Universitat de Barcelona, C/Casanova 143, 08036 Barcelona, Spain. lluisadeyebra@ub.edu
authors.forename: Lluïsa
authors.initials: L
authors.lastname: de Yebra
authors.forename: Rosa
authors.initials: R
authors.lastname: Adroer
authors.forename: Nuria
authors.initials: N
authors.lastname: de Gregorio-Rocasolano
authors.forename: Rafael
authors.initials: R
authors.lastname: Blesa
authors.forename: Ramon
authors.initials: R
authors.lastname: Trullas
authors.forename: Nicole
authors.initials: N
authors.lastname: Mahy
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D001345:Autoradiography; D001483:Base Sequence; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000235:genetics; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D053764:Presenilin-1; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; C500479:RABGAP1L protein, human; D012333:RNA, Messenger