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Updated: Jul 17, 2026

A Caenorhabditis elegans Model System for Amylopathy Study
Published on: May 17, 2013
APL-1, a Caenorhabditis elegans protein related to the human beta-amyloid precursor protein, is essential for
Angela Hornsten1, Jason Lieberthal, Shruti Fadia
1Program in Molecular Biology, Cell Biology, and Biochemistry, Boston University, Boston, MA 02215, USA.
Abstract:
Dominant mutations in the amyloid precursor protein (APP) gene are associated with rare cases of familial Alzheimer's disease; however, the normal functions of APP and related proteins remain unclear. The nematode Caenorhabditis elegans has a single APP-related gene, apl-1, that is expressed in multiple tissues. Loss of apl-1 disrupts several developmental processes, including molting and morphogenesis, and results in larval lethality. The apl-1 lethality can be rescued by neuronal expression of the extracellular domain of APL-1. These data highlight the importance of the extracellular domain of an APP family member and suggest that APL-1 acts noncell-autonomously during development. Overexpression of APL-1 also causes several defects, including a high level of larval lethality. Decreased activity of sel-12, a C. elegans homologue of the human gamma-secretase component presenilin 1, partially rescues the lethality associated with APL-1 overexpression, suggesting that SEL-12 activity regulates APL-1 activity either directly or indirectly.
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