PT  - JOURNAL ARTICLE
AU  - Neumann, Manuela
AU  - Sampathu, Deepak M.
AU  - Kwong, Linda K.
AU  - Truax, Adam C.
AU  - Micsenyi, Matthew C.
AU  - Chou, Thomas T.
AU  - Bruce, Jennifer
AU  - Schuck, Theresa
AU  - Grossman, Murray
AU  - Clark, Christopher M.
AU  - McCluskey, Leo F.
AU  - Miller, Bruce L.
AU  - Masliah, Eliezer
AU  - Mackenzie, Ian R.
AU  - Feldman, Howard
AU  - Feiden, Wolfgang
AU  - Kretzschmar, Hans A.
AU  - Trojanowski, John Q.
AU  - Lee, Virginia M.-Y.
TI  - Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
AID  - 10.1126/science.1134108
DP  - 2006 Oct 06
TA  - Science
PG  - 130--133
VI  - 314
IP  - 5796
4099  - http://science.sciencemag.org/content/314/5796/130.short
4100  - http://science.sciencemag.org/content/314/5796/130.full
SO  - Science2006 Oct 06; 314
AB  - Ubiquitin-positive, tau- and α-synuclein–negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.