Journal
ACTA NEUROPATHOLOGICA
Volume 114, Issue 3, Pages 221-229Publisher
SPRINGER
DOI: 10.1007/s00401-007-0261-2
Keywords
frontotemporal lobar degeneration; TDP-43; dementia with Lewy bodies; Parkinson's disease
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Funding
- NIA NIH HHS [P01 AG017586, AG-09215, P01 AG009215, AG-17586, AG-10124] Funding Source: Medline
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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 Do (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.
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