Motor neuron disease and frontotemporal lobar degeneration: a tale of two disorders linked to TDP-43.
Motor neuron disease (MND) is a neurodegenerative condition long thought to be associated only with motor weakness. Recent work now shows that cognitive difficulties are present in up to half of the patients with this disorder. About 5-10% of patients with MND have a frank dementia that resembles frontotemporal lobar degeneration (FTLD). Imaging studies show quantitative abnormalities that resemble FTLD. Moreover, biochemical studies of ubiquinated histopathologic abnormalities in MND and FTLD reveal identical inclusions of TDP-43. These findings underline a fundamental link between MND and FTLD. This paper reviews this body of work.
Elman
Lauren B
LB
Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. elmanl@uphs.upenn.edu
McCluskey
Leo
L
Grossman
Murray
M
D000368:Aged; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D004268:DNA-Binding Proteins