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Updated: Apr 3, 2026

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
Homodimerization Protects the Amyloid Precursor Protein C99 Fragment from Cleavage by γ-Secretase
Edith Winkler1, Ayse Julius2,3, Harald Steiner1,4
1BMC-Biomedical Center, Metabolic Biochemistry, Ludwig-Maximilians-University , Munich, Germany.
Abstract:
The amyloid precursor protein (APP) is a single-span integral membrane protein whose C-terminal fragment C99 is cleaved within the transmembrane helix by γ-secretase. Cleavage produces various Aβ peptides that are linked to the etiology of Alzheimer's disease. The transmembrane helix is known to homodimerize in a sequence-specific manner, and considerable controversy about whether the homodimeric form of C99 is cleaved by γ-secretase exists. Here, we generated various covalent C99 homodimers via cross-linking at engineered cysteine residues. None of the homodimers was cleaved in vitro by purified γ-secretase, strongly suggesting that homodimerization protects C99 from cleavage.
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