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

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

In the human brain, alternative splicing of amyloid precursor protein (APP) gene transcript generates at least three types of mRNA coding for APP 770 , APP 751 and APP 695 . 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 (APP 770 mRNA + APP 751 mRNA)/APP 695 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.

Original languageEnglish
Pages (from-to)303-310
Number of pages8
JournalMolecular Brain Research
Volume15
Issue number3-4
DOIs
Publication statusPublished - 01-01-1992

Fingerprint

Amyloid beta-Protein Precursor
Nervous System Diseases
Alzheimer Disease
Messenger RNA
Serine Proteinase Inhibitors
Amyloidogenic Proteins
RNA Precursors
Brain Diseases
Brain
Cerebrovascular Disorders
Amyloid beta-Peptides
Alternative Splicing
Frontal Lobe
Ribonucleases
Neurodegenerative Diseases

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Tanaka, Seigo ; Liu, Li ; Kimura, Jun ; Shiojiri, Satoshi ; Takahashi, Yasuyuki ; Kitaguchi, Nobuya ; Nakamura, Shigenobu ; Ueda, Kunihiro. / Age-related changes in the proportion of amyloid precursor protein mRNAs in Alzheimer's disease and other neurological disorders. In: Molecular Brain Research. 1992 ; Vol. 15, No. 3-4. pp. 303-310.
@article{04762094835948768d2db51f9fc29de1,
title = "Age-related changes in the proportion of amyloid precursor protein mRNAs in Alzheimer's disease and other neurological disorders",
abstract = "In the human brain, alternative splicing of amyloid precursor protein (APP) gene transcript generates at least three types of mRNA coding for APP 770 , APP 751 and APP 695 . 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 (APP 770 mRNA + APP 751 mRNA)/APP 695 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.",
author = "Seigo Tanaka and Li Liu and Jun Kimura and Satoshi Shiojiri and Yasuyuki Takahashi and Nobuya Kitaguchi and Shigenobu Nakamura and Kunihiro Ueda",
year = "1992",
month = "1",
day = "1",
doi = "10.1016/0169-328X(92)90122-R",
language = "English",
volume = "15",
pages = "303--310",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "3-4",

}

Age-related changes in the proportion of amyloid precursor protein mRNAs in Alzheimer's disease and other neurological disorders. / Tanaka, Seigo; Liu, Li; Kimura, Jun; Shiojiri, Satoshi; Takahashi, Yasuyuki; Kitaguchi, Nobuya; Nakamura, Shigenobu; Ueda, Kunihiro.

In: Molecular Brain Research, Vol. 15, No. 3-4, 01.01.1992, p. 303-310.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Age-related changes in the proportion of amyloid precursor protein mRNAs in Alzheimer's disease and other neurological disorders

AU - Tanaka, Seigo

AU - Liu, Li

AU - Kimura, Jun

AU - Shiojiri, Satoshi

AU - Takahashi, Yasuyuki

AU - Kitaguchi, Nobuya

AU - Nakamura, Shigenobu

AU - Ueda, Kunihiro

PY - 1992/1/1

Y1 - 1992/1/1

N2 - In the human brain, alternative splicing of amyloid precursor protein (APP) gene transcript generates at least three types of mRNA coding for APP 770 , APP 751 and APP 695 . 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 (APP 770 mRNA + APP 751 mRNA)/APP 695 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.

AB - In the human brain, alternative splicing of amyloid precursor protein (APP) gene transcript generates at least three types of mRNA coding for APP 770 , APP 751 and APP 695 . 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 (APP 770 mRNA + APP 751 mRNA)/APP 695 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.

UR - http://www.scopus.com/inward/record.url?scp=0026731205&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026731205&partnerID=8YFLogxK

U2 - 10.1016/0169-328X(92)90122-R

DO - 10.1016/0169-328X(92)90122-R

M3 - Article

VL - 15

SP - 303

EP - 310

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 3-4

ER -