TDP-43 pathology in a patient carrying G2019S LRRK2?mutation and a novel p.Q124E MAPT

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• 作者：Helen Ling ; Eleanna Kara ; Rina B ; opadhyay ; John Hardy ; Janice Holton ; Georgia Xiromerisiou ; Andrew Lees ; Henry Houlden ; Tamas Revesz
• 关键词：LRRK2 ; MAPT ; Parkinson's disease ; TDP-43 ; tau
• 刊名：Neurobiology of Aging
• 出版年：2013
• 出版时间：December, 2013
• 年：2013
• 卷：34
• 期：12
• 页码：2889.e5-2889.e9
• 全文大小：1059 K

文摘

Leucine-rich repeat kinase 2 (LRRK2) mutation is the most common cause of genetic-related parkinsonism and is usually associated with Lewy body pathology; however, tau, ¦Á-synuclein, and ubiquitin pathologies have also been reported. We report the case of a patient carrying the LRRK2 G2019S mutation and a novel heterozygous variant c.370C>G, p.Q124E in exon 4 of the microtubule-associated protein tau (MAPT). The patient developed parkinsonism with good levodopa response in her 70s. Neuropathological analysis revealed nigral degeneration and Alzheimer-type tau pathology without Lewy bodies. Immunohistochemical staining using phospho-TDP-43 antibodies identified occasional TDP-43 pathology in the hippocampus, temporal neocortex, striatum, and substantia nigra. However, TDP-43 pathology was not identified in another 4 archival LRRK2 G2019S cases with Lewy body pathology available in the Queen Square Brain Bank. Among other published cases of patients carrying LRRK2 G2019S mutation, only 3 were reportedly evaluated for TDP-43 pathology, and the results were negative. The role of the MAPT variant in the clinical and pathological manifestation in LRRK2 cases remains to be determined.