title: Development and characterization of an aged onset model of Alzheimer's disease in Drosophila melanogaster.
abstract: The biggest risk factor for developing Alzheimer's disease (AD) is age. Depending on the age of onset, AD is clinically categorized into either the early-onset form (before age 60years old), or the late-onset form (after age 65years old), with the vast majority of AD diagnosed as late onset (LOAD). LOAD is a progressive neurodegenerative disorder that involves the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles in the brains of elderly patients. Affected individuals often experience symptoms including memory loss, confusion, and behavioral changes. Though many animal models of AD exist, very few are capable of analyzing the effect of older age on AD pathology. In an attempt to better model LOAD, we developed a novel "aged AD" model using Drosophila melanogaster. In our model, we express low levels of the human AD proteins APP (amyloid precursor protein) and BACE1 (β-site APP cleaving enzyme BACE) specifically in the fly's central nervous system. Advantages of our model include the onset of behavioral and neuropathological symptoms later in the fly's lifespan due to a gradual accrual of Aβ within the central nervous system (CNS), making age the key factor in the behavioral and neuroanatomical phenotypes that we observe in this model.
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, USA.
authors.forename: Siddhita D
authors.initials: SD
authors.lastname: Mhatre
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Michelson
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, USA.
authors.forename: Janine
authors.initials: J
authors.lastname: Gomes
authors.affiliation: Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA, USA.
authors.forename: Loni Philip
authors.initials: LP
authors.lastname: Tabb
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, USA; Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA, USA; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: aleister.saunders@drexel.edu.
authors.forename: Aleister J
authors.initials: AJ
authors.lastname: Saunders
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, USA; Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: daniel.marenda@drexel.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Marenda
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D016282:Aspartic Acid Endopeptidases / Q000235:genetics; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008136:Longevity / Q000235:genetics; D009154:Mutation / Q000235:genetics; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D016827:CD8 Antigens; D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: APP; Alzheimer's disease; BACE; Drosophila; Late onset; Synapse