Abstract
Antibodies against APP, a precursor of Aβ deposited in Alzheimer's disease brain, have been shown to cause neuronal death. Therefore, it is important to determine whether Aβ mediates antibody-induced neurotoxicity. When primary neurons were treated with anti-APP antibodies, Aβ40 and Aβ42 in the cultured media were undetectable by an assay capable of detecting 100 nM Aβ peptides. However, exogenously treated Aβ1.42 or Aβ1-43 required >3 μM to exert neurotoxicity, and 25 μM Aβ1-40 was not neurotoxic. Glutathione-ethyl-ester inhibited neuronal death by anti-APP antibody, but not death by Aβ1-42, whereas serum attenuated toxicity by Aβ1-42, but not by anti-APP antibody. Using immortalized neuronal cells, we specified the domain responsible for toxicity to be cytoplasmic His657-Lys676, but not the Aβ1-42 region, of APP. This indicates that neuronal cell death by anti-APP antibody is not mediated by secreted Aβ.
| Original language | English |
|---|---|
| Pages (from-to) | 548-556 |
| Number of pages | 9 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 282 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2001 |
Fingerprint
Keywords
- Aβ polypeptide
- Alzheimer's disease
- Amyloid precursor protein
- Antibody-induced neuronal death
- Cytoplasmic domain
- Glutathione
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Secreted Aβ does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein. / Sudo, Haruka; Hashimoto, Yuichi; Niikura, Takako; Shao, Zongjun; Yasukawa, Takashi; Ito, Yuko; Yamada, Marina; Hata, Michihiro; Hiraki, Takako; Kawasumi, Masaoki; Koyama, Keisuke; Nishimoto, Ikuo.
In: Biochemical and Biophysical Research Communications, Vol. 282, No. 2, 2001, p. 548-556.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Secreted Aβ does not mediate neurotoxicity by antibody-stimulated amyloid precursor protein
AU - Sudo, Haruka
AU - Hashimoto, Yuichi
AU - Niikura, Takako
AU - Shao, Zongjun
AU - Yasukawa, Takashi
AU - Ito, Yuko
AU - Yamada, Marina
AU - Hata, Michihiro
AU - Hiraki, Takako
AU - Kawasumi, Masaoki
AU - Koyama, Keisuke
AU - Nishimoto, Ikuo
PY - 2001
Y1 - 2001
N2 - Antibodies against APP, a precursor of Aβ deposited in Alzheimer's disease brain, have been shown to cause neuronal death. Therefore, it is important to determine whether Aβ mediates antibody-induced neurotoxicity. When primary neurons were treated with anti-APP antibodies, Aβ40 and Aβ42 in the cultured media were undetectable by an assay capable of detecting 100 nM Aβ peptides. However, exogenously treated Aβ1.42 or Aβ1-43 required >3 μM to exert neurotoxicity, and 25 μM Aβ1-40 was not neurotoxic. Glutathione-ethyl-ester inhibited neuronal death by anti-APP antibody, but not death by Aβ1-42, whereas serum attenuated toxicity by Aβ1-42, but not by anti-APP antibody. Using immortalized neuronal cells, we specified the domain responsible for toxicity to be cytoplasmic His657-Lys676, but not the Aβ1-42 region, of APP. This indicates that neuronal cell death by anti-APP antibody is not mediated by secreted Aβ.
AB - Antibodies against APP, a precursor of Aβ deposited in Alzheimer's disease brain, have been shown to cause neuronal death. Therefore, it is important to determine whether Aβ mediates antibody-induced neurotoxicity. When primary neurons were treated with anti-APP antibodies, Aβ40 and Aβ42 in the cultured media were undetectable by an assay capable of detecting 100 nM Aβ peptides. However, exogenously treated Aβ1.42 or Aβ1-43 required >3 μM to exert neurotoxicity, and 25 μM Aβ1-40 was not neurotoxic. Glutathione-ethyl-ester inhibited neuronal death by anti-APP antibody, but not death by Aβ1-42, whereas serum attenuated toxicity by Aβ1-42, but not by anti-APP antibody. Using immortalized neuronal cells, we specified the domain responsible for toxicity to be cytoplasmic His657-Lys676, but not the Aβ1-42 region, of APP. This indicates that neuronal cell death by anti-APP antibody is not mediated by secreted Aβ.
KW - Aβ polypeptide
KW - Alzheimer's disease
KW - Amyloid precursor protein
KW - Antibody-induced neuronal death
KW - Cytoplasmic domain
KW - Glutathione
UR - http://www.scopus.com/inward/record.url?scp=0034741266&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034741266&partnerID=8YFLogxK
U2 - 10.1006/bbrc.2001.4604
DO - 10.1006/bbrc.2001.4604
M3 - Article
C2 - 11401495
AN - SCOPUS:0034741266
VL - 282
SP - 548
EP - 556
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -