title: 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.affiliation: 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.
authors.forename: Helen
authors.initials: H
authors.lastname: Ling
authors.forename: Eleanna
authors.initials: E
authors.lastname: Kara
authors.forename: Rina
authors.initials: R
authors.lastname: Bandopadhyay
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Janice
authors.initials: J
authors.lastname: Holton
authors.forename: Georgia
authors.initials: G
authors.lastname: Xiromerisiou
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D016631:Lewy Bodies; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C054369:MAPT protein, human; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: LRRK2; MAPT; Parkinson's disease; TDP-43; tau