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• W2036174583 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." @default.
• W2036174583 created "2016-06-24" @default.
• W2036174583 creator A5053905832 @default.
• W2036174583 creator A5080054480 @default.
• W2036174583 creator A5081814882 @default.
• W2036174583 date "2015-01-21" @default.
• W2036174583 modified "2023-10-18" @default.
• W2036174583 title "The Full-Length Form of the<i>Drosophila</i>Amyloid Precursor Protein Is Involved in Memory Formation" @default.
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• W2036174583 doi "https://doi.org/10.1523/jneurosci.2093-14.2015" @default.
• W2036174583 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6605540" @default.
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