2023-06-26 07:37:22
The “birth” of Alzheimer’s disease from the embryo? Subtle disturbances of a protein might induce vulnerabilities that only become apparent in adulthood following decades of biological stress.
What if Alzheimer’s disease left its mark on the embryo? Researchers from the Institut du Cerveau show that the amyloid precursor protein (APP) has a specific biological role during neurodevelopment; it delays the onset of neurogenesis, ie the differentiation of stem cells into different lines of nerve cells, which begins in the fetus from five weeks of gestation and is almost complete around 28 weeks. Until now, researchers did not know how this balance between proliferation of stem cells and differentiation into several cell types was regulated. To better understand how our brain is shaped during this key period, the researchers* carried out the investigation… It appears that subtle disturbances of this mechanism might, in certain individuals, induce vulnerabilities which only reveal themselves following adulthood following decades of biological stress. Alzheimer’s disease might then be considered as a neurodevelopmental disorder… with a particularly late onset. These results are published on June 6, 2023 in Science Advances.
APP, conductor of neural production
The regulatory role of APP is essential in the neurodevelopment of our species; to form, our brain needs to generate enormous quantities of neurons over a very long period and according to a very precise plan – the researchers observed that the process was not the same in mice where neurogenesis is very rapid -. So, in humans, abnormalities related to APP might cause premature neurogenesis and significant cellular stress, the consequences of which would be observable later, suggests Bassem Hassan, researcher at Inserm. Moreover, the brain regions in which the early signs of Alzheimer’s disease appear are also those whose maturation takes the longest during childhood and adolescence. »
Although the diagnosis of neurodegenerative diseases is usually made between the ages of 40 and 60, researchers estimate that the clinical signs appear several decades following the beginning of the decline of certain neuronal connections and populations. This loss of connectivity would itself reflect abnormalities at the molecular level present from childhood, or even earlier.
specific to the human species
New studies will be needed to confirm that APP holds a central place in the disturbances of neurodevelopment that make the bed of Alzheimer’s disease. In which case, one might consider that these disturbances lead to the formation of a brain that functions normally at birth, but is particularly vulnerable to certain biological events -such as inflammation, excitotoxicity or somatic mutations- and certain environmental factors such as diet, sleep, infections, etc., completes the researcher. Over time, these various stresses might lead to neurodegeneration, a phenomenon specific to the human species and made particularly visible by the lengthening of life expectancy. »
* Khadijeh Shabani and her colleagues from the “Brain Development” team led by Bassem Hassan (Inserm)
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