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

Neurobiol Aging 2013 Dec 9;34(12):2889.e5-9. Epub 2013 May 9.

Reta Lila Weston Institute of Neurological Studies and Queen Square Brain Bank for Neurological Disorders, Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK.

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, α-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.

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http://dx.doi.org/10.1016/j.neurobiolaging.2013.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906605PMC
December 2013
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