Table 3.

Experimental models of neurodegeneration

Disease	Animal model	Mechanism of neurodegeneration	References
Alzheimer’s disease	APP transgenic mice Transgenic mice expressing B secretase and APP, or presenilin-1 and APP	Increased APP deposition. Behavioural and, cognitive changes, amyloid pathology, increased, plaques and accumulation of Aβ	59,60
Parkinson’s disease	Mice overexpressing e.g. human alpha-synuclein Neurotoxins such as MPTP	Microglial activation. Adaptive immunity directed, to neurons expressing alpha-synuclein CD4+ T-cell-mediated damage	61–65
Stroke	MCAo, photothrombotic model (non-invasive)	Microglial TNF-α-induced neuronal damage Role for T cells and cytokines	66,67
Traumatic brain injury	Injury to brain or spinal cord	Neurons damaged close to activated microglia Pathogenic T and B cells induce neuronal injury	68,69
ALS	SOD-1 mutation Immunization with motor neurons	ER stress-related toxicity Autoimmune attack	70,71
Multiple sclerosis	Secondary progressive EAE in mice immunized,with spinal cord homogenate or MOG.,Outside-in model1 Spasticity in mice immunized with NF-L.,Inside-out model2 SFV, TMEV, MHV infections	Neuronal and axonal loss as a result of chronic inflammation. Heterogeneous mechanisms Direct attack on neurons and axons Loss of trophic support by myelin Heterogeneous mechanisms	27,72–77
Infectious
Viral	Human foamy virus – mice	Ataxia. Damage to cerebellar granule cells	78
	Tick-borne encephalitis virus – mice	Necrosis	79
	TMEV in mice	Virus-induced neuronal death, IFN-γ protects from neuronal death	80
	LP-BM5 murine leukaemia virus	Activation of AMPA receptors	80
	Mouse hepatitis virus	CD8+ T cells and antibodies	81
	LCMV – mice	Virus-induced neuronal death CD8+ T cells	82
	Murine retrovirus	Protein misfolding induces neuronal death	83
	Herpes simplex virus type 1	Neuronal cytoskeletal disruption	84
	Borna disease virus – rodents	Immune-mediated damage, glutamate excitotoxicity	85
Bacterial	Pneumococcal meningitis of mice	Spatial learning deficits in mice	86
Prion	Spongioform neurodegeneration	Prion protein aggregation activation of microglia	87
Parasitic	Toxoplasma gondii– mice	Immune-mediated neuronal loss	88

¹Outside-in model refers to siltation whereby myelin (on the outside) is damaged before axons (on the inside).

²Inside-out model refers to axonal/neuronal damage (inside) occurs prior to myelin damage.

Aβ, amyloid-beta; AMPA, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor; APP, amyloid precursor protein; EAE, experimental autoimmune encephalomyelitis; ER, endoplasmic reticulum; IFN-γ, interferon-γ; LCMV, lymphocytic choriomeningitis virus; MCAo, middle cerebral artery occlusion; MHV, murine hepatitis virus; MOG, myelin oligodendrocyte glycoprotein; NF-L, neurofilament light; SOD1, superoxide dismutase 1; SFV, Semliki Forest virus; TMEV, Theiler’s murine encephalomyelitis virus.