Pantothenate kinase‐associated neurodegeneration is not a synucleinopathy. Issue 2 (25th January 2013)

• Record Type: Journal Article
• Authors: Li, A.; Paudel, R.; Johnson, R.; Courtney, R.; Lees, A. J.; Holton, J. L.; Hardy, J.; Revesz, T.; Houlden, H.
• Is Part Of: Neuropathology & applied neurobiology. Volume 39:Issue 2(2013)
• Page Start: 121
• Page End: 131
• Publication Date: 2013-01-25
• Subjects: Nervous system -- Diseases -- Pathology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/j.1365-2990.2012.01269.x
• Languages: English
• ISSNs: 0305-1846

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A. Li, R. Paudel, R. Johnson, R. Courtney, A. J. Lees, J. L. Holton, J. Hardy, T. Revesz and H. Houlden (2013) <italic>Neuropathology and Applied Neurobiology</italic><bold>39, </bold> 121–131</p> <p> <bold>Pantothenate kinase‐associated neurodegeneration is not a synucleinopathy</bold> </p> <p> <bold>Aims:</bold> Mutations in the pantothenate kinase 2 gene (<italic>PANK2</italic>) are responsible for the most common type of neurodegeneration with brain iron accumulation (NBIA), known as pantothenate kinase‐associated neurodegeneration (PKAN). Historically, NBIA is considered a synucleinopathy with numerous reports of NBIA cases with Lewy bodies and Lewy neurites and some cases reporting additional abnormal tau accumulation. However, clinicopathological correlations in genetically proven PKAN cases are rare. We describe the clinical, genetic and neuropathological features of three unrelated PKAN cases. <bold>Methods:</bold> All three cases were genetically screened for the <italic>PANK2</italic> gene mutations using standard Sanger polymerase chain reaction sequencing. A detailed neuropathological assessment of the three cases was performed using histochemical and immunohistochemical preparations. <bold>Results:</bold> All cases had classical axonal swellings and Perls' positive iron deposition in the basal ganglia. In contrast to neuroaxonal dystrophies due to mutation of the phospholipase A2, group VI (<italic>PLA2G6</italic>) gene, in which Lewy body pathology is widespread, no α‐synuclein accumulation was detected in any of our PKAN cases. In one case (20‐year‐old male) there was significant tau pathology comprising neurofibrillary tangles and neuropil threads, with very subtle tau pathology in another case. <bold>Conclusions:</bold> These findings indicate that PKAN is not a synucleinopathy and, hence the cellular pathways implicated in this disease are unlikely to be relevant for the pathomechanism of Lewy body disorders.</p> </abstract>