Alteration in brain presenilin-1 mRNA expression in sporadic Alzheimer's disease.
Expression of presenilin-1 (PS-1) mRNA in an alternative splicing at the 3' end of exon 3 was examined in brain tissue, lymphocytes and cultured skin fibroblasts using the RT- polymerase chain reaction (RT-PCR) method. We quantified the relative ratios of the densities of the long form of PS-1 mRNA, which contains a sequence encoding four amino acids (VRSQ, denoted as VRSQ+) to the short form, which lacks the VRSQ sequence (VRSQ-). The brain tissue of subjects with sporadic Alzheimer's disease (AD) had reduced levels of the VRSQ+ form of the PS-1 mRNA compared to a control group. No significant differences appeared in peripheral tissues, such as lymphocytes or cultured skin fibroblasts in AD with control subjects. Changes in the alternative splicing of exon 3 may be specific to the brain and may play an important role in the pathogenesis of sporadic AD.
Division of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
K
K
Isoe-Wada
K
K
Urakami
Y
Y
Wakutani
Y
Y
Adachi
H
H
Arai
H
H
Sasaki
K
K
Nakashima
D000368:Aged; D017398:Alternative Splicing / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D005091:Exons / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D053764:Presenilin-1; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D012333:RNA, Messenger