title: Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases.
abstract: Here, we investigated if TAR-DNA-binding protein-43 (TDP-43), the disease protein in frontotemporal lobar degeneration and ubiquitin inclusions with or without motor neuron disease as well as amyotrophic lateral sclerosis, also formed inclusions in Lewy body (LB) disorders including Parkinson's disease (PD) without or with dementia (PDD), and dementia with LBs (DLB) alone or in association with Alzheimer's disease (AD). Immunohistochemical analyses of TDP-43 in clinically well characterized and pathologically confirmed cases of DLB + AD, PD and PDD demonstrated TDP-43 pathology in the following percentage of cases: DLB + AD = 25/80 (31.3%); PD = 5/69 (7.2%); PDD = 4/21 (19%), while DLB and normal controls exhibited no (0/10, 0%) and one cases (1/33, 3%) presenting TDP-43 pathology, respectively. Significant differences in the prevalence of TDP-43 lesions were noted between disease versus normal brains (P < 0.001) as well as demented versus non-demented brains (P < 0.001). Statistical analyses revealed a positive relationship between TDP-43 lesions and several clinical and pathological parameters in these disorders suggesting the TDP-43 pathology may have co-morbid effects in LB diseases. This study expands the concept of TDP-43 proteinopathies by implicating TDP-43 lesions in mechanisms of neurodegeneration in LB disorders.
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, HUP/Maloney 3rd Floor, Philadelphia, PA 19104-4283, USA.
authors.forename: Hanae
authors.initials: H
authors.lastname: Nakashima-Yasuda
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Uryu
authors.forename: John
authors.initials: J
authors.lastname: Robinson
authors.forename: Sharon X
authors.initials: SX
authors.lastname: Xie
authors.forename: Howard
authors.initials: H
authors.lastname: Hurtig
authors.forename: John E
authors.initials: JE
authors.lastname: Duda
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Andrew
authors.initials: A
authors.lastname: Siderowf
authors.forename: Murray
authors.initials: M
authors.lastname: Grossman
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.forename: Randy
authors.initials: R
authors.lastname: Woltjer
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.forename: Ronald
authors.initials: R
authors.lastname: Hamilton
authors.forename: Debby W
authors.initials: DW
authors.lastname: Tsuang
authors.forename: Douglas
authors.initials: D
authors.lastname: Galasko
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kaye
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Clark
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000368:Aged; D015897:Comorbidity; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D020961:Lewy Body Disease / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D025801:Ubiquitin; D051844:alpha-Synuclein; D016875:tau Proteins