Five specific neuron cell types in the motor cortex of the brain are most vulnerable to fatal neurodegenerative disease pathology.
Five specific subtypes of affected neuron cells in the motor cortex of the brain show the unique selective vulnerability to neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).(1✔ ✔Trusted Source
Brain Diseases: Certain Neurons Are Especially Susceptible to ALS and FTD
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While currently incurable, both the diseases share a common pathological signature ‘TDP-43 protein aggregates’ that clump within brain cells. ALS and FTD are linked neurodegenerative diseases causing paralysis and dementia.
The discovery was made by scientists at DZNE – German Center for Neurodegenerative Diseases and Ulm University Hospital. The research was published in Nature Communications.(2✔ ✔Trusted Source
Multi-modal dissection of cell-type specific TDP-43 pathology in the motor cortex
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The findings open new doors for tailored ALS and FTD therapies and more effective targeted neuroprotective treatments.
How Was Brain Tissue Analyzed to Identify Selective Neuron Vulnerability?
For their study, the research team led by Prof. Karin Danzer examined brain tissue from deceased patients with ALS, with a mixed form of ALS and FTD, as well as from individuals who had not shown neurological symptoms during their lifetime.
All samples came from the “motor cortex”, a brain area responsible for movement control. In total, neurons from around 80 individuals in Germany, the Netherlands, Scotland, and the United States were analyzed using advanced techniques.(3✔ ✔Trusted Source
Brain diseases: certain neurons are especially susceptible to ALS and FTD
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“In ALS, as well as in the mixed form of ALS and FTD, TDP-43 deposits occur in different regions of the brain. However, the motor cortex is particularly relevant for movement disorders, which is why we focused on this area,” explains Karin Danzer, a research group leader at DZNE’s Ulm site and at Ulm University Hospital.
Why Are Excitatory Neurons More Susceptible to Neurodegeneration?
The researchers found that not all neurons in this area are equally affected. “The protein aggregates occur predominantly within excitatory cells, that is, within neurons that serve to transmit and amplify nerve signals.”
“These cells seem to be particularly susceptible to the disease. This phenomenon is referred to as selective vulnerability and known for a long time in the field. In addition, within the affected neurons, we found five subgroups. Each of these is impacted by the disease in a specific way,” explains Danzer.
The findings are based on the “transcriptome” of affected neurons. This molecular fingerprint provides information about which genes are active in affected cells and therefore enable to distinguish pathological processes in different cells.
How Do Cell-Specific Changes Point to New Targets for Amyotrophic Lateral Sclerosis Therapy?
Based on this signature, the researchers were also able to identify cell type-specific changes. “Our data offer insights into disease mechanisms and thus point to possible targets for therapy development.”
“For example, one can see how the activity of certain genes is altered depending on the cell type.”
“The observation that not all neurons are equally affected suggests that future therapies will need to be tailored to specific cell types in order to combat the disease effectively,” says Danzer.
References:
- Brain Diseases: Certain Neurons Are Especially Susceptible to ALS and FTD – (https://www.dzne.de/en/im-fokus/meldungen/2026/brain-diseases-certain-neurons-are-especially-susceptible-to-als-and-ftd/)
- Multi-modal dissection of cell-type specific TDP-43 pathology in the motor cortex – (https://www.nature.com/articles/s41467-026-69944-6)
- Brain diseases: certain neurons are especially susceptible to ALS and FTD – (https://www.eurekalert.org/news-releases/1119702)
Source-Eurekalert