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Age-related changes of Alzheimer's disease-associated proteins in cynomolgus monkey brains.

Abstract：

:We characterized senile plaques (SPs) immunohistochemically in cynomolgus monkey brains and also examined age-related biochemical changes of Alzheimer's disease (AD)-associated proteins in these brains from monkeys of various ages. In the neocortex of aged monkeys (>20 years old), we found SPs but no neurofibrillary tangles (NFTs). Antibodies against beta-amyloid precursor protein (APP) or apolipoprotein E (ApoE) stained SPs; however, the pattern of immunostaining was different for the two antigens. APP was present only in swollen neurites, but ApoE was present throughout all parts of SPs. Western blot analysis revealed that the pattern of APP expression changed with age. Although full-length APP695 protein was mainly expressed in brains from young monkeys (4-years-old), the expression of full-length APP751 protein was increased in brains from older monkeys (>20 years old). Biochemical analyses also showed that levels of various AD-associated proteins increased significantly with age in nerve ending fractions. Both SP-associated (APP) and NFT-associated proteins (tau, activated glycogen synthase kinase 3beta, cyclin dependent kinase 5, p35, and p25) accumulated in the nerve ending fraction with increasing age; however, we found no NFTs or paired helical filaments of tau in aged cynomolgus monkey brains. This age-related accumulation of these proteins in the nerve ending fraction was similar to that observed in our laboratory previously for presenilin-1 (PS-1). The accumulation of these SP-associated proteins in this fraction may be a causal event in the spontaneous formation of SPs; thus, SPs may be formed initially in nerve endings. Taken together, these results suggest that intensive investigation of age-related changes in the nerve ending and in axonal transport will contribute to a better understanding of the pathogenesis of neurodegenerative disorders such as AD.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kimura N,Tanemura K,Nakamura S,Takashima A,Ono F,Sakakibara I,Ishii Y,Kyuwa S,Yoshikawa Y

doi

10.1016/j.bbrc.2003.09.012

subject

Has Abstract

pub_date

2003-10-17 00:00:00

pages

303-11

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006291X03017662

journal_volume

310

pub_type

杂志文章

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