Reverse relationship between β-amyloid precursor protein and β-amyloid peptide plaques in Down's syndrome versus sporadic/familial Alzheimer's disease

1999 ◽  
Vol 97 (2) ◽  
pp. 113-118 ◽  
Author(s):  
Rupert Egensperger ◽  
Sascha Weggen ◽  
Nobua Ida ◽  
Gerd Multhaup ◽  
Ralf Schnabel ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Down's Syndrome ◽  
Down’S Syndrome ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Familial Alzheimer’S Disease ◽  
Reverse Relationship ◽  
Β Amyloid ◽  
Familial Alzheimer's Disease ◽  
Β Amyloid Peptide

scholarly journals Syntaxin 5 interacts with presenilin holoproteins, but not with their N- or C-terminal fragments, and affects β-amyloid peptide production

2004 ◽  
Vol 381 (3) ◽  
pp. 619-628 ◽  
Author(s):  
Kei SUGA ◽  
Takami TOMIYAMA ◽  
Hiroshi MORI ◽  
Kimio AKAGAWA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Precursor Protein ◽  
Full Length ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Familial Alzheimer’S Disease ◽  
Aβ Amyloid ◽  
Β Amyloid ◽  
Familial Alzheimer's Disease

Mutations in presenilins 1 and 2 (PS1 and PS2) account for the majority of cases of early-onset familial Alzheimer's disease. However, the trafficking and interaction of PSs with other proteins in the early secretory pathways are poorly understood. Using co-immunoprecipitation, we found that PS bound to Syx5 (syntaxin 5), which is a target-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor involved in endoplasmic reticulum (ER)–Golgi vesicular transport in vivo. Syx5 interacted only with the full-length PS holoproteins and not with the naturally occurring N- or C-terminal fragments. The PS holoproteins co-immunoprecipitated with the mutant Syx5, which localized to the ER and Golgi compartments, despite the substitution of the transmembrane region with that of syntaxin 1A. In contrast, the transmembrane deletion mutant that localized to the cytosol, but not to the ER or Golgi compartments, did not co-immunoprecipitate the PS holoproteins. The PS1 variant linked to familial Alzheimer's disease (PS1ΔE9), lacking the region that contains the endoproteolytic cleavage site in the cytoplasmic loop, showed markedly decreased binding to Syx5. Immunofluorescence and sucrose-density-gradient fractionation analyses showed that the full-length PS holoproteins co-localized with Syx5 to the ER and cis-Golgi compartments. Furthermore, Syx5 overexpression resulted in the accumulation of PS holoproteins and the β-amyloid precursor protein, and reduced the secretion of the Aβ (amyloid β) peptide in COS-7 cells. In summary, these results indicate that Syx5 binds to full-length PSs and affects the processing and trafficking of β-amyloid precursor protein in the early secretory compartments.

scholarly journals Generation of the β-Amyloid Peptide and the Amyloid Precursor Protein C-terminal Fragment γ Are Potentiated by FE65L1

2003 ◽  
Vol 278 (51) ◽  
pp. 51100-51107 ◽  
Author(s):  
Yang Chang ◽  
Giuseppina Tesco ◽  
William J. Jeong ◽  
Loren Lindsley ◽  
Elizabeth A. Eckman ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Protein C ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Terminal Fragment ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Cytotoxic Fragment of Amyloid Precursor Protein Accumulates in Hippocampus after Global Forebrain Ischemia

1996 ◽  
Vol 16 (6) ◽  
pp. 1219-1223 ◽  
Author(s):  
Masayuki Yokota ◽  
Takaomi C. Saido ◽  
Eiichi Tani ◽  
Ikuya Yamaura ◽  
Nobutaka Minami
Keyword(s):  
Amyloid Precursor Protein ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Precursor Protein ◽  
Amyloid Peptide ◽  
Forebrain Ischemia ◽  
Ischemic Insult ◽  
Dentate Granule Cells ◽  
Β Amyloid ◽  
Β Amyloid Peptide

We developed an antibody specific to β-amyloid precursor protein (βAPP) fragments possessing the exact amino terminus of the β-amyloid peptide and examined its induction in postischemic hippocampus. In control hippocampus, this APP fragment was lightly observed in pyramidal neurons of CA sectors and dentate granule cells. Transient forebrain ischemia enhanced accumulation of the APP fragment in CA1 pyramidal neurons. Seven days after the ischemia, while the APP fragment was still observed in dentate granule cells and CA3 neurons, it disappeared in dead CA1 neurons. While astrocytes did not show in any immunoreactivity throughout the experiment, those in the CA1 sector showed moderate immunoreactivity 7 days after the ischemia. The APP fragment has a cytotoxic effect on cultured neurons. These results suggest that the accumulation of the cytotoxic APP fragment in CA1 neurons may play a role in the development of delayed neuronal death after the ischemic insult.

scholarly journals Elevation of β-Amyloid Peptide 2–42 in Sporadic and Familial Alzheimer's Disease and Its Generation in PS1 Knockout Cells

2001 ◽  
Vol 276 (46) ◽  
pp. 42645-42657 ◽  
Author(s):  
Jens Wiltfang ◽  
Hermann Esselmann ◽  
Philippe Cupers ◽  
Manuela Neumann ◽  
Hans Kretzschmar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Peptide ◽  
Familial Alzheimer’S Disease ◽  
Β Amyloid ◽  
Familial Alzheimer's Disease ◽  
Β Amyloid Peptide
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