Table 1.

Drosophila models of Alzheimer’s Disease.

Alzheimer’s Disease
Drosophila Model	Developmental Stage	Assay Used for Neuropathology	References
Drosophila orthologs of human genes
Pan–neuronal and photoreceptor–specific expression of Drosophila dBACE and APPL to produce dAβ	Adult	Toluidine blue histological staining for retinal degeneration, Thioflavin S staining for amyloid deposits, immunohistochemistry using anti–dAβ, fast phototaxis assay, TEM for fibrillary aggregates formation and degeneration	[40]
APPL null mutants	Adult	Histology for brain morphology, fast phototaxis assay, olfactory acuity assay, shock reactivity assay, odor conditioning assay, optomotor assay	[64]
Overexpression of human transgenes
Pan–neuronal and photoreceptor–specific expression of Aβ40 and Aβ42 fused to rat pre–proenkephalin signal peptide (SP)	Larva, Adult	Larvae: immunostaining and confocal microscopy for Aβ42 accumulation in imaginal eye discs Adult: SEM and light stereomicroscopy for eye morphology, lifespan, immunostaining with anti–Aβ (6E10) for Aβ42 accumulation, toluidine blue histological staining for ommatidial organization	[41]
Pan–neuronal expression of Aβ40, Aβ42 and Aβ42arc fused to Drosophila Necrotic protein SP	Adult	Lifespan, climbing assay, immunostaining with anti–Aβ (4G8) for Aβ42 accumulation, SEM for eye morphology	[42]
Photoreceptor–specific and mushroom body–specific expression of Aβ42 fused to Drosophila Argos SP	Adult	Light microscopy and SEM for retina structure, light microscopic histology of frontal eye sections for vacuolar degeneration, immunostaining and Thioflavin S staining for Aβ42 accumulation in eyes	[43]
Photoreceptor–specific expression of Aβ42 and blocking	Larva, Pupa, Adult	3rd Instar Larvae: immunostaining for eye imaginal disc development and Aβ42 accumulation, TUNEL staining for eye imaginal disc cell death, Pupae: immunostaining for eye development and Aβ42 accumulation Adult: immunostaining for eye development and Aβ42 accumulation, histology for photoreceptor morphology, SEM for eye morphology,	[44]
Expression of various mutated Aβ42 peptides for the effect of specific amino acid substitutions on toxicity	Adult	Lifespan, locomotor assay, immunohistochemistry using anti– Aβ42, Thioflavin T staining for rates of Aβ42 aggregation, TEM for Aβ42 aggregate morphology	[45]
Expression of various mutated Aβ42 peptides for the effect of specific amino acid substitutions on toxicity	Adult	Lifespan	[46]
Pan–neuronal and muscle–specific expression of Aβ42, exposure to exogenous Aβ42, and treatment with anti–Aβ42 antibody (6E10)	Larva	3rd Instar Larvae: Electrophysiology for synaptic transmission, FM1–43 dye imaging for neurotransmitter release, Thioflavin S staining for amyloid deposits	[47]
Pan–neuronal and photoreceptor–specific expression of two human Tau variants, manipulation of light exposure	Adult	Lifespan, histology, and light microscopy to quantify neurodegeneration, climbing assay, immunohistochemistry for pTau accumulation, light microscopy for eye morphology	[48]
Pan–neuronal expression of human APP and BACE1 separately and in combination, treatment with a γ–secretase inhibitor	Adult	Lifespan, fluorescence microscopy for defects in the whole–brain and mushroom body structure, immunostaining with anti– Aβ (6E10), Thioflavin S, and X–34 for amyloid deposition, climbing assay, conditioned courtship suppression assay	[57]
Expression of human BACE1 and late–onset induction of human APP	Adult	Lifespan, climbing assay, immunostaining with anti–Aβ (6E10) for amyloid deposition, fluorescence microscopy for defects in the whole–brain and mushroom body structure, conditioned courtship suppression assay	[58]
Combined models of Drosophila orthologs and overexpression of human transgenes
Knockdown of orthologs of human CD2AP, SNRPN, PTPRD, XYLT1, FERMT2, CELF1, ITGAM, ITGA9, MAST4 in Drosophila overexpressing human TauV337M	Adult	Light microscopy for eye morphology	[39]
Expression of Drosophila Psn, Drosophila APPL, human APP, and human BACE, separately and in combination	Adult	Histological staining for retinal degeneration, Thioflavin S and immunostaining with anti– Aβ (4G8) for Aβ accumulation in retinas, survival assay, lifespan	[20]
Aβ42arc overexpression, Draper inhibition, overexpression of Draper/MEGF10	Adult	Lifespan, Thioflavin S and anti–Aβ (6E10) immunostaining for Aβ, climbing assay, histological sectioning for vacuole quantification	[38]
Photoreceptor–specific expression of human Aβ42 in eyes, supplementation with zinc or copper, treatment with chelators, and overexpression of MTF–1	Larva, Adult	Larva: relative eclosion rate Adults: Stereomicroscopy for ommatidia structure, climbing assay	[50]
Pan–neuronal expression of Aβ42, treatment with an iron chelator, and RNAi knockdown of ferritin	Embryo, Adult	Embryos: Hatching efficiency assay Adults: Survival assay, Thioflavin T staining for amyloid aggregation	[49]
Photoreceptor–specific Aβ42 expression, over– and under–expression of an immunophilin, mutation in a copper transporter, and treatment with an exogenous copper chelator	Adult	Lifespan, light microscopy for eye morphology	[51]