Drosophila amyloid precursor protein-like is required for long-term memory.
The amyloid precursor protein (APP) plays an important role in Alzheimer's disease (AD), a progressive neurodegenerative pathology that first manifests as a decline of memory. While the main hypothesis for AD pathology centers on the proteolytic processing of APP, very little is known about the physiological function of the APP protein in the adult brain. Likewise, whether APP loss of function contributes to AD remains unclear. Drosophila has been used extensively as a model organism to study neuronal function and pathology. In addition, many of the molecular mechanisms underlying memory are thought to be conserved from flies to mammals, prompting us to study the function of APPL, the fly APP ortholog, during associative memory. It was previously shown that APPL expression is highly enriched in the mushroom bodies (MBs), a specialized brain structure involved in olfactory memory. We analyzed memory in flies in which APPL expression has been silenced specifically and transiently in the adult MBs. Our results show that in adult flies, APPL is not required for learning but is specifically involved in long-term memory, a long lasting memory whose formation requires de novo protein synthesis and is thought to require synaptic structural plasticity. These data support the hypothesis that disruption of normal APP function may contribute to early AD cognitive impairment.
Genes and Dynamics of Memory Systems, Neurobiology Unit, Centre National de la Recherche Scientifique, Ecole Supérieure de Physique et de Chimie Industrielles, 75005 Paris, France.
Valérie
V
Goguel
Anne-Laure
AL
Belair
Derya
D
Ayaz
Aurélie
A
Lampin-Saint-Amaux
Niki
N
Scaplehorn
Bassem A
BA
Hassan
Thomas
T
Preat
D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D057567:Memory, Long-Term / Q000502:physiology*; D024521:Mushroom Bodies / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000235:genetics / Q000378:metabolism*
C066839:Appl protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
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