Table 2.
Representative animal-model classes and their best use in dementia research.
| Model class | Illustrative examples | Best use | Main limitation |
|---|---|---|---|
| Amyloid transgenic | APP/PS1, 5xFAD | Aβ-centered synaptic and circuit mechanisms, early proteinopathy, and target-engagement studies | Non-physiological APP overexpression, familial mutations, and promoter/dosage artifacts limit sporadic late-life inference |
| Physiological-expression/late-onset risk models | App knock-in lines, humanized Aβ/tau platforms, MODEL-AD strains | Late-onset risk biology, age/sex/genetic-background modifiers, standardized phenotyping, and translatable biomarker alignment | Often slower, partial, or risk-factor-focused phenotypes; still require explicit pathology, circuit, and behavioral endpoint matching |
| Stereotaxic protein seeding/injection | Local Aβ oligomer/fibril infusion, tau seed injection | Local sufficiency, species/strain effects, regional vulnerability, propagation, and host-context modifier tests | Perturbation models; injection injury, dose/species selection, and acute timing limit claims about endogenous initiation or whole-syndrome dementia |
| Tau models | P301S, rTg4510 | Tau-related network failure, spread, and neurodegeneration-linked dysfunction | Do not capture the full biology of AD; some lines also carry model-specific artifacts |
| Vascular/hypoperfusion | BCAS and related chronic hypoperfusion paradigms | VCID mechanisms, white-matter disconnection, and mixed-pathology cumulative-burden contrasts | BCAS can produce broad hypoperfusion; AD-specific inference requires measured proteinopathy, vascular readouts, and topographic interpretation |
| Inflammation models | LPS exposure, immune priming paradigms | Immune sufficiency/modulation tests and stage-dependent inflammatory effects | Low AD specificity when used alone |
| Aged animals | Aged wild-type mice, aged rats | Aging, reserve/resilience, frailty, and comorbidity background effects | Low pathology specificity |
| Non-mammalian models | Drosophila, zebrafish | Rapid genetic screening and pathway discovery | Weak syndrome-level translation to human dementia |
| NHP/companion animals | Non-human primates, dogs | Aging and cognition face validity, longer-horizon phenotypes, and comparative translational anchoring | Ethical constraints, high cost, and typically small sample sizes |
The purpose is orienting rather than taxonomic: the same nominal class can support stronger or weaker claims depending on age, background strain, outcome selection, and whether mixed-pathology features are measured.
AD, Alzheimer's disease; BCAS, bilateral common carotid artery stenosis; LPS, lipopolysaccharide; NHP, non-human primate; VCID, vascular cognitive impairment and dementia.