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

Abstract

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.

• Authors: Helen Ling, Eleanna Kara, Rina Bandopadhyay, John Hardy, Janice Holton, Georgia Xiromerisiou, Andrew Lees, Henry Houlden, Tamas Revesz
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 34 Issue 12 Pg. 2889.e5-9 (Dec 2013) ISSN: 1558-1497 [Electronic] United States
• PMID: 23664753 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• DNA-Binding Proteins
• MAPT protein, human
• tau Proteins
• LRRK2 protein, human
• Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
• Protein Serine-Threonine Kinases

Topics

• Aged
• Aged, 80 and over
• Brain (metabolism)
• DNA-Binding Proteins (metabolism)
• Exons (genetics)
• Female
• Frontotemporal Lobar Degeneration (genetics)
• Heterozygote
• Humans
• Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
• Lewy Bodies
• Mutation
• Parkinson Disease (genetics, pathology)
• Protein Serine-Threonine Kinases (genetics)
• tau Proteins (genetics)