Table 1.

Drosophila model of Alzheimer’s disease.

	DROSOPHILA MODEL		STAGE OF NEUROPATHOLOGICAL ASSESMENT	ASSAY EMPLOYED FOR NEUROPATHOLOGICAL ASSESSMENT	KEY ACHIEVEMENTS	REFERENCES
DROSOPHILA ORTHOLOGS OF HUMAN GENES
	Null mutants of APPL		Adult	Histological analysis, phototaxis assay, olfactory acuity assay, shock reactivity, odor conditioning, optomotor assay	Established the role of APPL in brain morphology and behavior, providing insights into neurodegeneration mechanisms	[273]
	Pan-neuronal and photoreceptor-specific expression of Drosophila dBACE (Drosophila β-secretase) and APPL (Amyloid precursor protein-like) in Drosophila results in the production of dAβ (Drosophila amyloid beta).		Adult	Histological analysis, Thioflavin S staining, immunohistochemistry, phototaxis assay, TEM	Demonstrated the role of amyloid-beta in retinal degeneration, contributing to understanding AD pathology	[70]
INCREASED EXPRESSION OF HUMAN TRANSGENES
	Expression of Aβ40, Aβ42, and Aβ42arc fused to Drosophila Necrotic protein signal peptide (SP) specifically in pan-neuronal cells		Adult	Lifespan measurement, climbing assay, immunostaining, SEM	Identified Aβ42 accumulation’s contribution to AD pathology and its potential as a target for therapeutic intervention	[52]
	Expression of Aβ40 and Aβ42 fused to rat pre-proenkephalin signal peptide (SP) specifically in pan-neuronal and photoreceptor cells.		Larva, Adult	In larvae, immunostaining coupled with confocal microscopy was utilized to visualize Aβ42 accumulation specifically in the imaginal eye discs. For adults, eye morphology was examined using scanning electron microscopy (SEM) and light stereomicroscopy. Lifespan assays were conducted to monitor longevity. Immunostaining with anti-Aβ (6E10) antibodies was employed to detect Aβ42 accumulation in adult eyes. Additionally, toluidine blue histological staining was used to assess the organization of ommatidia in the adult eye tissue.	Demonstrated the role of Aβ42 in eye tissue organization and neurodegeneration, highlighting its potential as a therapeutic target	[53]
	Studying the effects of particular amino acid changes on toxicity by expressing various mutated forms of Aβ42 peptides		Adult	Assessment of lifespan, locomotor function, immunohistochemistry employing anti-Aβ42 antibodies, Thioflavin T staining to quantify rates of Aβ42 aggregation, and transmission electron microscopy (TEM) for examining the morphology of Aβ42 aggregates.	Established the impact of specific mutations on Aβ42 aggregation and neurotoxicity, providing insights into the mechanisms of AD pathology	[71]
	Expression specifically targeted to photoreceptor cells of Aβ42, with an additional blocking function.		Larva, Pupa, Adult	In the third instar larvae stage, immunostaining was conducted to assess eye imaginal disc development and Aβ42 accumulation, while TUNEL staining was utilized to detect cell death in the eye imaginal disc. In the pupal stage, immunostaining was performed to examine eye development and Aβ42 accumulation. Upon reaching adulthood, immunostaining continues to evaluate eye development and Aβ42 accumulation. Additionally, histological analysis was conducted to assess photoreceptor morphology, and SEM was employed to study eye morphology.	Identified the protective effects of targeted blocking functions against Aβ42-induced degeneration in photoreceptor cells, offering potential therapeutic strategies	[72]
	Exploring the effects of specific amino acid substitutions on toxicity through the expression of a variety of mutated Aβ42 peptides		Adult	Lifespan	Clarified the effects of amino acid substitutions on peptide toxicity and aggregation rates, advancing the understanding of mutation-driven neurodegenerative processes	[73]
	Expression of Aβ42 specifically in pan-neuronal and muscle cells, exposure to externally applied Aβ42, and administration of anti-Aβ42 antibody (6E10) treatment		Larva	In third instar larvae, electrophysiology was conducted to assess synaptic transmission, FM1-43 dye imaging was used to visualize neurotransmitter release, and Thioflavin S staining is performed to detect amyloid deposits.	Highlighted the impact of extracellular Aβ42 on synaptic function and the therapeutic potential of anti-Aβ42 antibodies	[74]
	Expression of human amyloid precursor protein (APP) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) separately and together specifically in pan-neuronal cells, along with treatment using a γ-secretase inhibitor		Adult	Lifespan assessment, climbing ability, immunostaining, TEM	Revealed interaction between APP and BACE1, informing therapeutic strategies targeting amyloid production	[75]
	Expression of two human Tau variants specifically in pan-neuronal and photoreceptor cells, along with manipulation of light exposure		Adult	Lifespan measurement, histological examination, climbing assay, immunohistochemistry, light microscopy	Provided evidence for Tau-induced neurodegeneration and its modulation by light exposure, guiding future studies on Tau-targeted therapies	[76]
	The presence of human beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) expression and the delayed activation of human amyloid precursor protein (APP) are linked to conditions characterized by late onset		Adult	Measurement of lifespan, climbing ability assessment, immunostaining using anti-Aβ (6E10) to detect amyloid deposition, fluorescence microscopy to identify abnormalities in whole-brain structure	Provided evidence of the role of BACE1 in amyloid deposition and its effects on neurodegeneration and climbing ability	[77]
INTEGRATION OF DROSOPHILA ORTHOLOG MODELS WITH THE OVEREXPRESSION OF HUMAN TRANSGENES
	Downregulation of the orthologs corresponding to human SNRPN, FERMT2, ITGA9, CD2AP, CELF1, PTPRD, MAST4, XYLT1, ITGAM in Drosophila, while concurrently overexpressing human TauV337M		Adult	Examination of eye morphology using light microscopy	Demonstrated the combined impact of gene downregulation and Tau overexpression on eye morphology, contributing to understanding tauopathies	[78]
	Expression of Aβ42 specifically in pan-neuronal cells, treatment with an iron chelator, and RNA interference (RNAi) targeting ferritin for knockdown		Embryo, Adult	For embryos: conducting a hatching efficiency assay. For adults: performing a survival assay and using Thioflavin T staining to assess amyloid aggregation	Showcased the role of iron in enhancing Aβ42 toxicity and the potential of iron chelation as a therapeutic strategy	[79]
	Overexpression of Aβ42arc, inhibition of Draper, and overexpression of Draper/MEGF10		Adult	Assessment of lifespan, Thioflavin S staining and immunostaining using anti-Aβ (6E10) antibody for Aβ detection, climbing assay and histological sectioning for quantifying vacuoles	Highlighted the influence of Draper on Aβ42 toxicity and its regulation of neurodegenerative processes	[80]
	Expression of human Aβ42 specifically in photoreceptor cells within the eyes, along with supplementation with zinc or copper, administration of chelators, and overexpression of MTF-1		Larva, Adult	For larvae: assessment of relative eclosion rate. For adults: examination of ommatidia structure using stereomicroscopy, along with conducting climbing assays.	Identified the role of zinc and copper in Aβ42 toxicity and the neuroprotective effects of metal chelation and MTF-1 overexpression	[81]
	Expression of Aβ42 specifically in photoreceptor cells, modulation of immunophilin expression (both overexpression and underexpression)		Adult	Assessment of lifespan and examination of eye morphology using light microscopy	Demonstrated the impact of immunophilin expression on Aβ42-induced neurodegeneration in photoreceptor cells	[82]