Table 1.

Considerations when modeling idiopathic PD in rodents.

Feature	AAV-overexpression models	α-syn PFF model
Ability to examine impact of α-synuclein inclusions distinct from degeneration	Difficult	Straightforward
	Simultaneous α-syn overexpression and aggregation progresses rapidly to degeneration over the course of weeks	Distinct interval of inclusion formation followed by degeneration over a protracted time course
Injection artifact	Confound	Less of a factor
	Direct injections into the SN produce marked neuroinflammatory response that can make interpretation difficult	Direct injections into the striatum have less of an impact within the SN
α-synuclein levels	Not analogous to idiopathic PD	Normal endogenous α-syn levels
	Continuous supraphysiological α-syn levels produced by forced overexpression are not analogous to idiopathic PD	Pathophysiology results from templating of normal levels of α-syn
Extranigral α-synuclein pathology	Not present	α-syn pathology in multiple regions
	Pathology limited to the nigrostriatal system	Allows for the examination of events outside of nigrostriatal system

Abbreviations: AAV, adeno-associated virus; α-syn, alpha-synuclein; PD, Parkinson’s disease; PFFs, alpha-synuclein preformed fibrils; SN, substantia nigra.