Scientists at the University of Southern California have found that people with frontotemporal dementia may have structural brain differences that begin before birth, even if symptoms of this type of dementia appear in middle age or later. Research published in the journal Cell Reports.
Up to 10% of frontotemporal dementia and amyotrophic lateral sclerosis (ALS) cases are caused by mutations in the C9ORF72 gene, but these diseases have different symptoms. ALS, also known as Lou Gehrig’s disease, gradually causes the patient’s paralysis and respiratory arrest, and frontotemporal dementia changes behavior, personality, and speech.
Both diseases are usually diagnosed in middle age or later, but carriers of the C9ORF72 mutation may experience a reduction in size of two brain regions, the thalamic region and frontal cortex, decades before the onset of any symptoms. In a new study, scientists found that these changes can be detected at the embryonic stage.
The biologists conducted experiments on the skin and blood cells of patients with the C9ORF72 mutation and diagnosed with frontotemporal dementia or ALS. They reprogrammed them into stem cells of the nervous system, which are responsible for its formation during embryonic development. Compared to healthy people, neural stem cells from patients with ALS or frontotemporal dementia failed to proliferate. Instead, they often evolved into mature neurons prematurely.
As the scientists discovered, this was because the stem cells obtained from the patients contained a mutant protein called polyAP.
Experiments in mice showed that mutations in C9ORF72 cause measurable developmental changes not only in the brain but also in other parts of the animal’s body during the embryonic stage. Their thalamic regions have shrunk and the thickness of the cerebral cortex has also decreased. In addition, the weight of 18-day embryos was 5-10% less than normal.
“We are just beginning to understand how the development of the nervous system in the embryo may contribute to neurodegeneration in the adult. Our results suggest that C9ORF72 mutations impair neurodevelopment in the womb in patients with ALS and frontotemporal dementia, and this may potentially contribute to the onset of disease symptoms later in life.” stressed the authors.
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