Two neurodegenerative diseases have the same cause
Researchers at the University of Pennsylvania have identified a misfolded protein that is deposited in the neurons of patients with amyotrophic lateral sclerosis and frontal lobe dementia. In the first case, the protein TDP-43 forms aggregates in motoneurons of the spinal cord and brainstem, in the second case in the frontal and temporal lobes of the brain.
The scientists around Virginia Lee had examined the deposits already known for both neurodegenerative diseases in more detail, which are similar to those of Alzheimer's disease but consist of different proteins. In the autopsied brains, they discovered misfolded TDP-43 in the inclusions. These results suggest that amyotrophic lateral sclerosis, also known as Lou Gehring's disease, and frontal lobe dementia are distinct manifestations of the same molecular cause.
In amyotrophic lateral sclerosis, motor neuron failure causes problems with walking, eating, speaking and even breathing, resulting in paralysis and eventually death. Frontal lobe dementia, on the other hand, is the most common cause of mental decline before the age of 65 after Alzheimer's disease. In contrast to Alzheimer's dementia, the typical symptoms initially appear as disinhibited and socially inappropriate behavior and personality changes, but then also memory loss.
Normally, TDP-43 probably regulates DNA transcription in the cell nucleus and also functions as a structural protein. It is still unclear whether the disease symptoms are due to the deposits themselves or due to the failure of TDP-43 to function.