Table 2.

Neuropathology of Mendelian genetic forms of Parkinson’s disease

Locus/gene	Mutation	Neuropathology	References
PARK1,4/SNCA	p.A53T, p.A30P, p.E46 K	Nigral neuronal loss, cortical and brainstem Lewy bodies	[22, 35, 121, 136]
	SNCA triplication/duplication	Cortical and brainstem Lewy bodies, temporal lobe vacuolation.	[25, 84, 90]
PARK2/PARKIN	Exon4Del/Exon4Del p.K211 N/Exon4Del p.Q34fs/p.Q34fs	Nigral neuronal loss, no Lewy bodies	[37, 43, 83, 128]
	Exon3Del/Exon3Del	Nigral neuronal loss, no Lewy bodies, α-synuclein positive inclusions in the pedunculopontine nucleus	[108]
	p.R275W/p.Pro113fsX51	Cortical Lewy bodies, none in the brainstem but occasional Lewy neurites in the dorsal nucleus of vagus.	[24]
	Del1072T/Exon7Del	Lewy bodies in the locus ceruleus and substantia nigra	[103]
PARK8/LRRK2	p.G2019S	Neuropathology ranges from non-specific nigral degeneration to widespread Lewy body disease.	[30, 32, 58, 106]
	p.R1441C	Varies from Lewy body disease to nigral degeneration with ubiquitin positive inclusions to severe tau pathology	[139]
	p.R1441G/p.I2020T	Non-specific nigral degeneration	[27, 77]
	p.Y1699C	Varies from Lewy body disease to nigral degeneration with ubiquitin positive inclusions or Alzheimer pathology	[58, 139]
PARK6/PINK1	Exon7Del/c.1488 + 1G > A	Nigral neuronal loss, Lewy bodies and aberrant neurites in the reticular nuclei of the brainstem, substantia nigra pars compacta and Meynert nucleus.	[107]
PARK14/ PLA2G6	p.R37X/c.1078–3C>A p.T572I/p.T572I	Range from mild to severe Lewy body disease, with neurofibrillary tangles and axonal speroids	[94]
PANK2	p.G521R/p.G521R	No Lewy bodies, diffuse tau pathology	[60]

Neuropathology is grouped according to mutation