BACKGROUND: ATP13A2 (PARK9) loss of function mutations are a genetic cause of an 
early-onset form of Parkinson's disease (PD), with in vitro studies showing that 
ATP13A2 deficits lead to lysosomal and mitochondrial dysfunction and α-synuclein 
accumulation, while elevated ATP13A2 expression reduces α-synuclein toxicity. 
The three human brain tissue studies assessing changes in ATP13A2 expression in 
PD produced divergent results; mRNA is increased while protein levels were 
observed to be either increased or decreased. This apparent conflict in protein 
levels might have arisen from examining Lewy body disease cases with coexisting 
Alzheimer-type pathologies.To assess whether ATP13A2 levels in Lewy body disease 
are modified by Alzheimer-type β-amyloid deposition, we evaluated cases of pure 
PD and pure dementia with Lewy bodies (DLB) for changes in ATP13A2, α-synuclein 
and β-amyloid protein levels in cortical regions with and without Lewy bodies.
RESULTS: In all Lewy body disease cases, we identified decreased ATP13A2 protein 
levels that correlated with increases in both α-synuclein and β-amyloid. Partial 
colocalization was observed between ATP13A2 and α-synuclein in Lewy bodies, 
whereas ATP13A2 did not colocalize with pathological β-amyloid deposition.
CONCLUSIONS: Our data show that patients with Lewy body diseases have an overall 
deficit in ATP13A2 protein levels, with the remaining protein being more 
insoluble and partially redistributing towards Lewy bodies. This supports the 
concept that increasing ATP13A2 levels may offer potential therapeutic benefits 
to patients with Lewy body diseases.