Abstract
The cerebral amyloid deposited in Alzheimer's disease (AD) contains a 4.2 kDa β amyloid polypeptide (AP) that is derived from a larger β amyloid protein precursor (APP). Three APP mRNAs encoding proteins of 695, 751, and 770 amino acids have previously been identified. In each of these, there is a single membrane-spanning domain close to the carboxyl-terminus of the APP, and the 42 amino acid AP sequence extends from within the membrane-spanning domain into the large extracellular region of the APP. We raised rabbit antisera to a peptide corresponding to amino acids 45-62 near the aminoterminus of the APP. We show that these antisera detect the APP by demonstrating that they (i) label a set of ∼120 kDa membrane-associated proteins in human brain previously detected by antisera to the carboxyl-terminus of APP and (ii) label a set of ∼120 kDa membrane-associated proteins that are selectively overexpressed in cells transfected with a full length APP expression construct. The APP45-62 antisera specifically stain senile plaques in AD brains. This finding, along with the previous demonstration that antisera to the carboxyl-terminus of the APP label senile plaques, indicates that both near amino-terminal and carboxyl-terminal domains of the APP are present in senile plaques and suggests that proteolytic processing of the full length APP molecule into insoluble amyloid fibrils occurs in a highly localized fashion at the sites of amyloid deposition in AD brains.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 432-437 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 156 |
| Issue number | 1 |
| DOIs | |
| State | Published - Oct 14 1988 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
Antisera to an amino-terminal peptide detect the amyloid protein precursor of alzheimer's disease and recognize senile plaques. / Palmert, Mark R.; Podlisny, Marcia Berman; Witker, Dennis S.; Oltersdorf, Tilman; Younkin, Linda H.; Selkoe, Dennis J.; Younkin, Steven G.
In: Biochemical and Biophysical Research Communications, Vol. 156, No. 1, 14.10.1988, p. 432-437.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antisera to an amino-terminal peptide detect the amyloid protein precursor of alzheimer's disease and recognize senile plaques
AU - Palmert, Mark R.
AU - Podlisny, Marcia Berman
AU - Witker, Dennis S.
AU - Oltersdorf, Tilman
AU - Younkin, Linda H.
AU - Selkoe, Dennis J.
AU - Younkin, Steven G
PY - 1988/10/14
Y1 - 1988/10/14
N2 - The cerebral amyloid deposited in Alzheimer's disease (AD) contains a 4.2 kDa β amyloid polypeptide (AP) that is derived from a larger β amyloid protein precursor (APP). Three APP mRNAs encoding proteins of 695, 751, and 770 amino acids have previously been identified. In each of these, there is a single membrane-spanning domain close to the carboxyl-terminus of the APP, and the 42 amino acid AP sequence extends from within the membrane-spanning domain into the large extracellular region of the APP. We raised rabbit antisera to a peptide corresponding to amino acids 45-62 near the aminoterminus of the APP. We show that these antisera detect the APP by demonstrating that they (i) label a set of ∼120 kDa membrane-associated proteins in human brain previously detected by antisera to the carboxyl-terminus of APP and (ii) label a set of ∼120 kDa membrane-associated proteins that are selectively overexpressed in cells transfected with a full length APP expression construct. The APP45-62 antisera specifically stain senile plaques in AD brains. This finding, along with the previous demonstration that antisera to the carboxyl-terminus of the APP label senile plaques, indicates that both near amino-terminal and carboxyl-terminal domains of the APP are present in senile plaques and suggests that proteolytic processing of the full length APP molecule into insoluble amyloid fibrils occurs in a highly localized fashion at the sites of amyloid deposition in AD brains.
AB - The cerebral amyloid deposited in Alzheimer's disease (AD) contains a 4.2 kDa β amyloid polypeptide (AP) that is derived from a larger β amyloid protein precursor (APP). Three APP mRNAs encoding proteins of 695, 751, and 770 amino acids have previously been identified. In each of these, there is a single membrane-spanning domain close to the carboxyl-terminus of the APP, and the 42 amino acid AP sequence extends from within the membrane-spanning domain into the large extracellular region of the APP. We raised rabbit antisera to a peptide corresponding to amino acids 45-62 near the aminoterminus of the APP. We show that these antisera detect the APP by demonstrating that they (i) label a set of ∼120 kDa membrane-associated proteins in human brain previously detected by antisera to the carboxyl-terminus of APP and (ii) label a set of ∼120 kDa membrane-associated proteins that are selectively overexpressed in cells transfected with a full length APP expression construct. The APP45-62 antisera specifically stain senile plaques in AD brains. This finding, along with the previous demonstration that antisera to the carboxyl-terminus of the APP label senile plaques, indicates that both near amino-terminal and carboxyl-terminal domains of the APP are present in senile plaques and suggests that proteolytic processing of the full length APP molecule into insoluble amyloid fibrils occurs in a highly localized fashion at the sites of amyloid deposition in AD brains.
UR - http://www.scopus.com/inward/record.url?scp=0023729858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023729858&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(88)80859-3
DO - 10.1016/S0006-291X(88)80859-3
M3 - Article
C2 - 3140814
AN - SCOPUS:0023729858
VL - 156
SP - 432
EP - 437
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -