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Pantothenate kinase-associated neurodegeneration is not a synucleinopathy

Li, A; Paudel, R; Johnson, R; Courtney, R; Lees, AJ; Holton, JL; Hardy, J; ... Houlden, H; + view all (2013) Pantothenate kinase-associated neurodegeneration is not a synucleinopathy. Neuropathology and Applied Neurobiology , 39 (2) pp. 121-131. 10.1111/j.1365-2990.2012.01269.x. Green open access

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Abstract

Aims:  Mutations in the pantothenate kinase 2 gene (PANK2) 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. Methods:  All three cases were genetically screened for the PANK2 gene mutations using standard Sanger PCR sequencing. A detailed neuropathological assessment of the three cases was performed using histochemical and immunohistochemical preparations. Results:  All cases had classical axonal swellings and Perl's positive iron deposition in the basal ganglia. In contrast to neuroaxonal dystrophies due to mutation of the phospholipase A2, group VI (PLA2G6) gene, in which Lewy body (LB) 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. Conclusions:  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. © 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.

Type: Article
Title: Pantothenate kinase-associated neurodegeneration is not a synucleinopathy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/j.1365-2990.2012.01269.x
Publisher version: http://dx.doi.org/10.1111/j.1365-2990.2012.01269.x
Language: English
Additional information: © 1999-2013 John Wiley & Sons, Inc. All Rights Reserved.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: http://discovery.ucl.ac.uk/id/eprint/1344694
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