Antisera to an amino-terminal peptide detect the amyloid protein precursor of alzheimer's disease and recognize senile plaques

Mark R. Palmert, Marcia Berman Podlisny, Dennis S. Witker, Tilman Oltersdorf, Linda H. Younkin, Dennis J. Selkoe, Steven G Younkin

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)432-437
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume156
Issue number1
DOIs
StatePublished - Oct 14 1988
Externally publishedYes

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Amyloid beta-Protein Precursor
Amyloid Plaques
Immune Sera
Alzheimer Disease
Peptides
Amyloid
Labels
Brain
Amino Acids
Membrane Proteins
Membranes
Coloring Agents
Demonstrations
Rabbits

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 journalArticle

Palmert, Mark R. ; Podlisny, Marcia Berman ; Witker, Dennis S. ; Oltersdorf, Tilman ; Younkin, Linda H. ; Selkoe, Dennis J. ; Younkin, Steven G. / Antisera to an amino-terminal peptide detect the amyloid protein precursor of alzheimer's disease and recognize senile plaques. In: Biochemical and Biophysical Research Communications. 1988 ; Vol. 156, No. 1. pp. 432-437.
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