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Brain & Nervous System Health Center

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Protein Clue for Lou Gehrig's Disease

Lou Gehrig's Disease and a Type of Dementia Share Key Protein
WebMD Health News
Reviewed by Louise Chang, MD

Oct. 5, 2006 -- Lou Gehrig's disease and a certain type of dementia appear to have something in common: a protein called TDP-43.

The finding may "accelerate efforts to develop better therapies for these disorders," write the researchers.

They included Manuela Neumann, MD, and Virginia Lee, PhD, of the University of Pennsylvania.

Lou Gehrig's disease is also called amyotrophic lateral sclerosis ( ALS ALS). Lou Gehrig was a famous baseball player who died of the motor neuron disease in 1941. Motor neuron diseases affect the nerves that control muscles.

In ALS, the nerve cells (neurons) of the brain and spinal cord that control voluntary muscle movement gradually deteriorate, eventually leading to muscle wasting, paralysis, and death.

Frontotemporal lobar degeneration is a type of dementia. The terms "frontotemporal" or "frontotemporal lobar" refer to certain brain areas.

Frontotemporal dementias are the second most common type of dementia in people age 65 and younger, note Neumann and colleagues.

Protein Link

The researchers had long suspected that ALS and frontotemporal lobar dementia might have something in common. But until now, they hadn't found the link.

They studied brain tissue from 72 patients who had died with dementia and/or motor neuron diseases, including 47 with frontotemporal lobar degeneration and 19 with ALS.

After a series of lab tests, the researchers identified TDP-43 as the tie between the two conditions.

"It's very exciting that we finally made the connection between dementia and motor neuron disease," Lee says in a University of Pennsylvania news release.

TDP-43 is found throughout the body. It's a type of disease protein that has "been identified in many neurodegenerative disorders," the researchers write.

Ordinarily, another protein, called ubiquitin, works to prevent the buildup of disease proteins in the body.

But in ALS and frontotemporal lobar degeneration, that process goes awry, so TDP-43 builds up in the brain and spinal cord.

TDP-43 is "the major disease protein in both disorders," write Neumann, Lee, and colleagues.

The discovery doesn't solve all the mysteries of how dementia and ALS work. But it could be a clue in the hunt for new treatments, the researchers note.

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