Table 6 Quick guide to the pros and cons of commonly used AD mouse models

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]

APP^NLF

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]

APP^NLGF

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]