Simple model systems reveal conserved mechanisms of Alzheimer’s disease and related tauopathies

Table 1 Genetic modifier screens in S. cerevisiae, C. elegans and D. melanogaster models of Alzheimer’s disease

Organism	Transgene	Screen	Phenotype	Reference
S. cerevisiae	secretory GAL-α-prepro- Aβ_42-GFP	yeast deletion collection of ∼6000 ORFs	growth	[93]
S. cerevisiae	secretory GAL-Kar2- Aβ₄₂	overexpression library of 5532 full-length ORFs	growth	[297]
S. cerevisiae	secretory GPD-Kar2- Aβ₄₂	~ 4300 deletion and ~ 1200 temperature sensitive mutant strains	growth	[42]
C. elegans	myo-3p::Aβ₄₂ (muscle)	RNAi against 7970 C. elegans genes with human homologs	paralysis	[154]
C. elegans	aex3::hTau V337M (pan neuronal)	RNAi against 16,757 genes	uncoordinated (Unc) locomotion	[165]
Drosophila	Aβ₄₂ expressed in the eye	1963 EP insertions^a	rough eye phenotype	[30]
Drosophila	Aβ₄₂ expressed in central nervous system	3000 GS insertions^a	longevity	[255]
Drosophila	hTauV337M expressed in the eye	2276 EP insertions	rough eye phenotype	[274]
Drosophila	hTauV337M expressed in the eye	RNAi sequences for 87 fly homologs of human candidate genes	rough eye phenotype	[275]
Drosophila	hTau expressed in the eye	RNAi sequences for 74 fly homologs of human candidate genes	quantification of eye size	[66]
Drosophila	hTau expressed in the eye	144 Drosophila miRNAs	quantification of eye size	[285]
Drosophila	hTauV337M expressed in the eye	1250 P{Mae-UAS.6.11} insertion^a	rough eye phenotype	[17]
Drosophila	hTau expressed in the eye	RNAi sequences targeting 2,645 Drosophila genes	rough eye phenotype	[156]

^aEP, GS (Gene Search), and P{Mae-UAS.6.11} lines contain gene insertions that allow forced expression of genes using the GAL4-UAS system, they typically result in over or mis-expression of the associated gene but can also result in loss of function

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