Table 6.

Quick guide to the pros and cons of commonly used AD mouse models

Model	Main features	Pros	Cons	Examples of use in AD research
Tg2576	mid-life amyloid pathology (10–14 mo)	well-characterized, maintains aging feature of AD	high lethality on C57 background, Tg male aggressive and needs to be single-housed	[222–224]
APP/PS1	early-onset (~6 mo) amyloid pathology	well-characterized, co-integrated transgenes breed as a single allele	like other co-integrated models, cannot control for independent transgene effects	[225–227]
5XFAD	juvenile-onset amyloid pathology (~3 mo)	rapid onset phenotype, co-integrated transgenes breed as a single allele	non-physiological combination of FAD mutations, marked intracellular Aβ accumulation	[228–230]
3xTg-AD	early- to mid-life amyloid pathology plus hyperphosphorylated tau	captures both Aβ and phospho-tau features of AD	variable pathology between colonies and sexes, genetic drift has been observed	[231–233]
rTg4510	early-onset neurofibrillary tangles (~5–6 mo), severe neurodegeneration	temporally controllable, rapid onset phenotype, develops true NFT pathology, well-characterized	breeding complicated by need for two independent transgenes, 13-fold overexpression of tau protein	[67, 234, 235]
PS19	mid-life neurofibrillary tangles (6–9 mo), marked neurodegeneration	single-transgenic model, mid-life onset allows use in experiments expected to either delay or exacerbate pathology	transgene expression in spinal cord causes paralysis by mid-life	[236–238]
APPNLF	mid-life amyloid pathology (~12 mo for homozygote, but note >24 mo for heterozygote allele)	endogenous APP level, native human Aβ sequence	limited cognitive impairment, requires homozygous allele for mid-life onset	[59, 239]
APPNLGF	juvenile-onset amyloid pathology (~3–4 mo for homozygote, ~9 mo for heterozygote)	endogenous APP level, can be used as heterozygote	non-native Aβ sequence, mild cognitive phenotype	[60, 240]
hTau	mid-life hyperphosphorylated tau (~6 mo)	near-endogenous level expression of all 6 human wild-type tau isoforms	complicated breeding of transgene on null background, mild phenotype variable between colonies	[81, 82]
APOE2, E3, E4 Targeted replacement	allele-specific effects on Aβ, tau, brain atrophy, and neuroinflammation; both central and peripheral functions influenced by allele	widely-studied, expressed at endogenous levels, mouse ApoE deleted	cannot distinguish central vs. peripheral effects; available through Taconic but with restrictions on usage	[201, 241]