Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases.
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.
Nakashima-Yasuda
Hanae
H
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.
Uryu
Kunihiro
K
Robinson
John
J
Xie
Sharon X
SX
Hurtig
Howard
H
Duda
John E
JE
Arnold
Steven E
SE
Siderowf
Andrew
A
Grossman
Murray
M
Leverenz
James B
JB
Woltjer
Randy
R
Lopez
Oscar L
OL
Hamilton
Ronald
R
Tsuang
Debby W
DW
Galasko
Douglas
D
Masliah
Eliezer
E
Kaye
Jeffrey
J
Clark
Christopher M
CM
Montine
Thomas J
TJ
Lee
Virginia M-Y
VM
Trojanowski
John Q
JQ
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
D004268:DNA-Binding Proteins; D025801:Ubiquitin; D051844:alpha-Synuclein; D016875:tau Proteins