Protein Suggests ALS,
Frontotemporal Degeneration Linked

Scientists in the United States, Canada and Germany report in the Oct. 6 issue of the journal Science that they have uncovered what may be an important link between amyotrophic lateral sclerosis (ALS) and the cognitive disorder known as frontotemporal lobar degeneration.

Both diseases are characterized by abnormal clumps (inclusions) of proteins in nerve cell and, now, these inclusions have been found to contain a protein called TDP-43 in both disorders.

In ALS, the principal site of damage is the motor (muscle-controlling) nerve cells in the brain and spinal cord. In frontotemporal lobar degeneration, the cells responsible for thinking and feeling in the frontal and temporal lobes of the brain sustain the most damage.

The researchers, coordinated by Virginia Lee at the University of Pennsylvania School of Medicine in Philadelphia, say their findings suggest that “these diseases may represent a spectrum of disorders that share similar pathological mechanisms, culminating in the progressive degeneration of different selectively vulnerable neurons.”

Recently, mutations in the gene for the CHMP2B protein were found to cause two cases of ALS and to cause frontotemporal dementia (confusion) in a Danish family, providing another link between these two disease types. However, the vast majority of ALS cases have not been linked to specific genetic mutations.

In an editorial accompanying the Oct. 6 paper, Robert Brown, who directs the MDA/ALS Center at Massachusetts Hospital in Boston, says the new finding “means that we have some clue of what distinguishes ALS neurons [nerve cells] as being abnormal.”

The function of TDP-43 is murky, although scientists have speculated that it may be a regulator of gene activity or be a structural protein or perhaps both.