Table 2. NHP models of NDs generated by gene manipulation.

Model	Targeted gene	Method	Pathology	Phenotype	References
PD	α-Synuclein	Substantia injection	Lewy body, DA neuronal loss	Head bias	Kirik et al., 2003; Koprich et al., 2016
		Transgenic by embryo injection	α-Synuclein, accumulation	Age-dependent fine motor deficits, anxiety, cognitive impairments	Niu et al., 2015
	PINK1	Gene disruption by CRISPR/Cas9 at embryo stage	Massive neuronal loss	Neurodevelopment dysfunction	Yang et al., 2019c, 2022
	PINK+DJ1	Gene disruption by CRISPR/Cas9 by substantia injection	Lewy body, DA neuronal degeneration, inflammation	Typical hemi-parkinsonism	Li et al., 2021b
AD	Tau	Overexpression of mutant human Tau by entorhinal cortex injection	Elevated inflammatory molecules and pTau, NFL in CSF and blood, Tau hyperphosphorylation and spread along circuitry network	Not available	Beckman et al., 2021
	Aβ	Serial injection of human AβOs into hippocampus of aged animals	Massive Aβ plaque across brain, overt intracellular Tau hyperphosphorylation	Not investigated	Yue et al., 2021
ALS	TDP-43	Overexpression of mutant human TDP-43 by lateral cerebral injection	TDP-43 accumulation in cytoplasm, salient neurodegeneration	Contralateral paralysis	Yin et al., 2019
HD	Htt	Transgenic by embryo injection of mutant Htt	CAG repeat dependent neuron inclusion and neurodegeneration	Prominent progressive motor function impairment	Yang et al., 2008a
		Overexpression of mutant human Htt by lateral striatum injection	Overt intracellular aggregates, mild neurodegeneration	Mild motor deficits	Weiss et al., 2022