Table 1.

Mendelian Genes that Lead to Parkinsonism and Their Pathology

Locus	Genes	Clinical Features	Pathology
Dominant
PARK1/4	α-Synuclein	Typical PD but can sometimes have a dementia presentation	Lewy bodies
PARK8	LRRK2	Typical PD	Usually Lewy bodies: sometime tangles, sometimes neither
FTDP-17	MAPT	Most mutations have a dementia phenotype but some have a typical PD presentation	Tau/tangle pathology
SCA3	Ataxin3	Usually ataxia in Europeans, but often Parkinsonian especially in Africans	Probably not Lewy bodies. Probably polyglutamine inclusions
SCA2	Ataxin2	Usually ataxia in Europeans, but often Parkinsonian especially in Asians	Probably not Lewy bodies. Probably polyglutamine inclusions
Recessive
PARK2	Parkin	Very slowly progressive early onset disease usually with sleep benefit	Usually not Lewy bodies
PARK6	PINK1	Usually very slowly progressive early onset disease usually with sleep benefit	One case with Lewy bodies
PARK7	DJ-1	Little data, but seems similar to parkin	Not known
PARK9	ATP13A2	Aggressive and complex parkinsonism with many additional features	Not known
PARK14	PLA2G6	Aggressive and complex parkinsonism with many additional features	Lewy bodies
SPG11	Spatacsin	Usually spastic paraplegia but sometimes aggressive and complex parkinsonism with additional features	Not known
High-Risk Locus
Gaucher's (1) locus	GBA	Typical PD	Lewy bodies
Low-Risk Loci
	SNCA	Typical PD	Lewy bodies
	MAPT		Lewy bodies (though tau pathology not systematically assessed
	LRRK2	Typical PD	Lewy bodies
	HLA	Typical PD	Lewy bodies