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Updated: Jun 3, 2026

Purification and Aggregation of the Amyloid Precursor Protein Intracellular Domain
Published on: August 28, 2012
The intracellular threonine of amyloid precursor protein that is essential for docking of Pin1 is dispensable for
Alessia P M Barbagallo1, Zilai Wang, Hui Zheng
1Department of Microbiology and Immunology, Einstein College of Medicine, Bronx, New York, United States of America.
Background:
Processing of Aβ-precursor protein (APP) plays an important role in Alzheimer's Disease (AD) pathogenesis. Thr residue at amino acid 668 of the APP intracellular domain (AID) is highly conserved. When phosphorylated, this residue generates a binding site for Pin1. The interaction of APP with Pin1 has been involved in AD pathogenesis.
Methodology/Principal Findings:
To dissect the functions of this sequence in vivo, we created an APP knock-in allele, in which Thr(668) is replaced by an Ala (T(668)A). Doubly deficient APP/APP-like protein 2 (APLP2) mice present postnatal lethality and neuromuscular synapse defects. Previous work has shown that the APP intracellular domain is necessary for preventing early lethality and neuromuscular junctions (NMJ) defects. Crossing the T(668)A allele into the APLP2 knockout background showed that mutation of Thr(668) does not cause a defective phenotype. Notably, the T(668)A mutant APP is able to bind Mint1.
Conclusions/Significance:
Our results argue against an important role of the Thr(668) residue in the essential function of APP in developmental regulation. Furthermore, they indicate that phosphorylation at this residue is not functionally involved in those APP-mediated functions that prevent (NMJ) defects and early lethality in APLP2 null mice.
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