Down's syndrome: up-regulation of beta-amyloid protein precursor and tau mRNAs and their defective coordination.
Almost all patients > 40 years of age with Down's syndrome (DS) develop the pathology characteristic of Alzheimer's disease: abundant beta-amyloid plaques and neurofibrillary tangles. We have investigated the gene expression of beta-amyloid protein precursor (APP) and tau in DS and age-matched control brains and found that levels of both mRNAs were significantly elevated in DS. Such up-regulation was not observed in two other neuronal proteins. A correlation between total APP and tau mRNA levels was also found in DS brain but distinct from the pattern observed in normal brain. Although a proportionality existed between APP-695 mRNA and three-repeat tau mRNA in DS, the proportionality between APP-751 mRNA and four-repeat tau mRNA, which is normally present, was not observed. Thus, DS brains are primarily characterized by the up-regulation of tau mRNA as well as APP mRNA and disruption of the coordinate expression between APP-751 and four-repeat tau.
Oyama
F
F
Division of Biomedical Polymer Science, School of Medicine, Fujita Health University, Aichi, Japan.
Cairns
N J
NJ
Shimada
H
H
Oyama
R
R
Titani
K
K
Ihara
Y
Y
D000328:Adult; D000368:Aged; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007536:Isomerism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D012091:Repetitive Sequences, Nucleic Acid; D016875:tau Proteins / Q000235:genetics*
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D016875:tau Proteins