Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations

NEUROBIOLOGY OF AGING

卷:33

Article

Paisan-Ruiz, Coro¹  Li, Abi^1,2  Schneider, Susanne A.³  Holton, Janice L.^1,2  Johnson, Robert⁵  Kidd, Desmond⁶  Chataway, Jeremy⁶  Bhatia, Kailash P.³  Lees, Andrew J.⁴  Hardy, John¹  Revesz, Tamas^1,2  Houlden, Henry¹ 

[1] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England

[2] UCL Inst Neurol, Queen Sq Brain Bank, London WC1N 3BG, England

[3] UCL Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England

[4] Rita Lila Weston Inst Neurol Studies, London, England

[5] Univ Maryland, Dept Pediat, Baltimore, MD USA

[6] Royal Free & Univ Coll Med Sch, Dept Clin Neurosci, London WC1E 6BT, England

关键词: PLA2G6;    PANK2;    Lewy bodies;    tau;    parkinsonism;   

DOI  :  10.1016/j.neurobiolaging.2010.05.009

来源: Elsevier

【 摘 要 】

The 2 major types of neurodegeneration with brain iron accumulation (NBIA) are the pantothenate kinase type 2 (PANK2)-associated neurodegeneration (PKAN) and NBIA2 or infantile neuroaxonal dystrophy (INAD) due to mutations in the phospholipase A2, group VI (PLA2G6) gene. We have recently demonstrated clinical heterogeneity in patients with mutations in the PLA2G6 gene by identifying a poorly defined subgroup of patients who present late with dystonia and parkinsonism. We report the clinical and genetic features of 7 cases with PLA2G6 mutations. Brain was available in 5 cases with an age of death ranging from 8 to 36 years and showed widespread alpha-synuclein-positive Lewy pathology, which was particularly severe in the neocortex, indicating that the Lewy pathology spread corresponded to Braak stage 6 and was that of the diffuse neocortical type. In 3 cases there was hyperphosphorylated tau accumulation in both cellular processes as threads and neuronal perikarya as pretangles and neurofibrillary tangles. Later onset cases tended to have less tau involvement but still severe alpha-synuclein pathology. The clinical and neuropathological features clearly represent a link between PLA2G6 and parkinsonian disorders. (C) 2012 Elsevier Inc. All rights reserved.

【 授权许可】

Free