Table 2.

Non-transgenic mouse models of Alzheimer’s disease.

Model	Description	Outcome	Plaques	NFTs	Neuron loss	Synaptic deficits	Memory deficits	Notes	Example	References
Non-transgenic
Acute Aβ injection	Direct infusion of Aβ into the brain (e.g. dorsal hippocampi, lateral ventricles)	Acute local Aβ elevation	NO	NO	NO	YES	YES	Aβ source/preparation/conformation is crucial	Cell-derived Aβ, Aβ dimers from human brain, 200 nM synthetic Aβ oligomers	Walsh et al. 2002 Nature; Shankar et al. 2008 Nat Med; Puzzo et al. 2012 Neurobiol Aging; Watterson et al. 2013 PLOS One; Fiorito et al. 2013 Eur J Med Chem [21, 30, 32–34]
Acute tau injection	Direct infusion of tau into the brain (e.g. dorsal hippocampi)	Acute local tau elevation	NO	NO	NO	YES	YES	Different tau isoforms can be used, as well as naturally-derived tau from brain extracts	Tau oligomers from human brain, recombinant tau oligomers	Moe et al. 2008, 2009, 2010, 2010; Lasagna-Reeves et al. 2012 Sci Reports [71, 101–104]
Aged animal models	Aged mice, rats, dogs, non-human primates	Natural age-related deficits	YES (dogs, non-human primates)	NO	NO	YES	YES	Exhibit cognitive deficits, brain hypermetabolism, cholinergic defects, altered calcium homeostasis, oxidative stress, neophobia.	Aged mice (>18–20 months old)	Gallagher et al. 1993 Behav Brain Res; Gower et al. 1993 Behav Brain Res [72, 73]
Senescence-accelerated prone mice (SAMP8)	Spontaneously mutated inbred mouse strain	Shortened lifespan and accelerated aging phenotype; elevated levels of endogenous APP and Aβ	NO	NO	NO	YES	YES	Some tau hyperphosphorylation along with decreased spine density and synaptic proteins; increased gliosis and oxidative stress.	SAMP8	Yagi et al. 1988 Brain Res; Okuma et al. 1998 Jpn J Pharmacol [74, 75]