Mutations of TARDBP gene have been shown to cause Amyotrophic Lateral Sclerosis and have been reported to present with clinical heterogeneity including parkinsonism.
The high prevalence of TDP-43 inclusions in the substantia nigra is a relatively new finding and is probably related to the relatively high prevalence of parkinsonism in C9ORF72-positive patients.
Our findings suggest that the clinical presentation of the p.A382TTARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset.
Mutations of the TARDBP gene encoding TDP-43 protein have been shown to cause amyotrophic lateral sclerosis and have been reported to present with clinical heterogeneity including parkinsonism.
In conclusion, we expand the clinical spectrum associated with TARDBP mutations to FTLD with parkinsonism without motoneuron disease and to clinically definite PD.
Four hundred thirty-four patients with FTD, including primary progressive aphasia, semantic dementia, FTD/amyotrophic lateral sclerosis (ALS), FTD/motor neuron disease, corticobasal syndrome/corticobasal degeneration, progressive supranuclear palsy, Pick disease, dementia lacking distinctive histopathology, and pathologically confirmed cases of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U); and 111 non-FTD cases (controls) in which TDP-43 deposits were a prominent neuropathological feature, including subjects with ALS, Guam ALS and/or parkinsonism dementia complex, Guam dementia, Alzheimer disease, multiple system atrophy, and argyrophilic grain disease.
However, it has been reported more recently that TDP-43 positive inclusions occur in other neurodegenerative disorders such as Alzheimer's disease, Dementia with Lewy Bodies and Parkinsonism dementia complex of Guam.