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ATP13A2 (PARK9) protein levels are reduced in brain tissue of cases with Lewy bodies


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 alpha-synuclein accumulation, while elevated ATP13A2 expression reduces alpha-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 beta-amyloid deposition, we evaluated cases of pure PD and pure dementia with Lewy bodies (DLB) for changes in ATP13A2, alpha-synuclein and beta-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 alpha-synuclein and beta-amyloid. Partial colocalization was observed between ATP13A2 and alpha-synuclein in Lewy bodies, whereas ATP13A2 did not colocalize with pathological beta-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.

Type Journal
ISBN 2051-5960 (Electronic) 2051-5960 (Linking)
Authors Murphy, K. E.; Cottle, L.; Gysbers, A. M.; Cooper, A. A.; Halliday, G. M.;
Garvan Authors A/Prof Antony Cooper
Published Date 2013-12-01 00:00:00
Published Volume 1
Published Issue 1
Published Pages 11
Status Published In-print
OpenAccess Link