Skip to Content
Merck
  • The full-length form of the Drosophila amyloid precursor protein is involved in memory formation.

The full-length form of the Drosophila amyloid precursor protein is involved in memory formation.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2015-01-23)
Isabelle Bourdet, Thomas Preat, Valérie Goguel
ABSTRACT

The APP plays a central role in AD, a pathology that first manifests as a memory decline. Understanding the role of APP in normal cognition is fundamental in understanding the progression of AD, and mammalian studies have pointed to a role of secreted APPα in memory. In Drosophila, we recently showed that APPL, the fly APP ortholog, is required for associative memory. In the present study, we aimed to characterize which form of APPL is involved in this process. We show that expression of a secreted-APPL form in the mushroom bodies, the center for olfactory memory, is able to rescue the memory deficit caused by APPL partial loss of function. We next assessed the impact on memory of the Drosophila α-secretase kuzbanian (KUZ), the enzyme initiating the nonamyloidogenic pathway that produces secreted APPLα. Strikingly, KUZ overexpression not only failed to rescue the memory deficit caused by APPL loss of function, it exacerbated this deficit. We further show that in addition to an increase in secreted-APPL forms, KUZ overexpression caused a decrease of membrane-bound full-length species that could explain the memory deficit. Indeed, we observed that transient expression of a constitutive membrane-bound mutant APPL form is sufficient to rescue the memory deficit caused by APPL reduction, revealing for the first time a role of full-length APPL in memory formation. Our data demonstrate that, in addition to secreted APPL, the noncleaved form is involved in memory, raising the possibility that secreted and full-length APPL act together in memory processes.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
3-Octanol, 99%
Supelco
Acrylamide, analytical standard
Sigma-Aldrich
Acrylamide, for Northern and Southern blotting, powder blend
Sigma-Aldrich
Acrylamide, purum, ≥98.0% (GC)
Sigma-Aldrich
3-Octanol, ≥97%, FCC, FG
Sigma-Aldrich
3-Octanol, natural, ≥97%, FCC, FG
Sigma-Aldrich
Acrylamide, suitable for electrophoresis, ≥99% (HPLC), powder
Sigma-Aldrich
Acrylamide, suitable for electrophoresis, ≥99%
Supelco
Acrylamide, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
Acrylamide, for molecular biology, ≥99% (HPLC)
Sigma-Aldrich
4-Methylcyclohexanol, mixture of cis and trans, 98%
Supelco
3-Octanol, analytical standard
Supelco
Acrylamide solution, 40% in H2O, for molecular biology
Sigma-Aldrich
Acrylamide solution, 40%, suitable for electrophoresis, sterile-filtered
Sigma-Aldrich
Anti-α-Tubulin antibody, Mouse monoclonal, clone DM1A, purified from hybridoma cell culture