Age-related changes in the proportion of amyloid precursor protein mRNAs in Alzheimer's disease and other neurological disorders

Seigo Tanaka, Li Liu, Jun Kimura, Satoshi Shiojiri, Yasuyuki Takahashi, Nobuya Kitaguchi, Shigenobu Nakamura, Kunihiro Ueda

研究成果: Article査読

44 被引用数 (Scopus)

抄録

In the human brain, alternative splicing of amyloid precursor protein (APP) gene transcript generates at least three types of mRNA coding for APP770, APP751 and APP695. The former two types harbor, but the latter one lacks a domain of Kunitz-type serine protease inhibitor (KPI). We studied, by using the RNase protection technique, the expression of APP mRNAs in brains of Alzheimer's disease (AD) and other neurological disorders with special reference to aging. We found that the ratio of (APP770 mRNA + APP751 mRNA)/APP695 mRNA in the frontal cortex increased approximately 1.5-fold in AD compared with other neurodegenerative or cerebrovascular disorders. The ratio in other neurological disorders did not change significantly from control even in their affected brain regions. On the other hand, we found a positive correlation between the ratio and age; the ratio (y) increased gradually with the advance of age (x) as expressed by y = 0.005x + 0.014 (r = 0.372) for the AD group, and y = 0.004x - 0.037 (r = 0.486) for the non-AD group. These correlations indicate that the AD brain reached the same ratio of KPI-harboring to lacking APP mRNAs a few decades earlier than the non-AD brain in senescence. This finding of AD-specific and age-related change led us to the idea that a relative increase in KPI-harboring APPs over a KPI-lacking APP may perturb normal degradation of APPs, thereby leading to deposition of βA4 protein as amyloid.

本文言語English
ページ(範囲)303-310
ページ数8
ジャーナルMolecular Brain Research
15
3-4
DOI
出版ステータスPublished - 10-1992

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞および分子神経科学

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