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
N1 - Funding Information:
AcknowledgemenTtsh. is workw as supportebdy Grants-in-Aida nda SpeciaGl rantfor Clinical Investigatiofnro mthe Ministryo f Education, Sciencea nd Culture,J apan, and a grant from the Sasagawa HealthS cienceF oundationW. e thankD rs.M. Kameyam(aS umitomo Hospital),T . Takeda( Kyoto Universitya) nd K. Uragami( Tottori Universityf)o r usefuld iscussiona, nd Dr.B .R. Das (Instituteo f Life SciencesI,n dia)f or collaborativweo rk.Drs. M. OgawaF, . Udaka,K . Hara and R. Matsumoto(K yoto University-affiliatehdo spitalsa) re gratefullya cknowledgefodr providingu s withb rainsamples.
PY - 1992/10
Y1 - 1992/10
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0026731205
UR - https://www.scopus.com/pages/publications/0026731205#tab=citedBy
U2 - 10.1016/0169-328X(92)90122-R
DO - 10.1016/0169-328X(92)90122-R
M3 - Article
C2 - 1331685
AN - SCOPUS:0026731205
SN - 0169-328X
VL - 15
SP - 303
EP - 310
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 3-4
ER -
