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The deactivation of two genes could be the cause of Alzheimer’s


Alzheimer’s disease could be caused by the deactivation of what are known as “presenilin genes”. Using mice as a model for the study of Alzheimer’s in humans, a scientific team headed by the researcher Carlos Saura, from the Universitat Autònoma de Barcelona, has discovered that when these genes mutate and stop working they cause neuro-degeneration and memory loss, giving rise to what in humans would be Alzheimer’s. The discovery, published in Neuron, is totally unexpected, since up till now it was thought that the alteration that caused Alzheimer’s was exactly the opposite, that is to say, an excess of presenilin activity.

Since 1995 it has been known that family hereditary Alzheimer’s is caused mainly by mutations in presenilin genes, but it was thought that the alteration of these genes caused Alzheimer’s due to an increase in their activity. Research by doctor Carlos Saura, of the Neuroscientific Institute (l’Institut de Neurociències (IN)) at the Universitat Autònoma de Barcelona, using mice, genetically modified to decrease the activity of presenilin genes, has shown that these genes take part in the process of memory consolidation and neuron survival, but in a different way to that expected.

The results, published in the journal Neuron last April, show that the absence of activity of these genes in mice, used as a model for the study of Alzheimer’s in humans, causes symptoms very similar to those observed in persons suffering from Alzheimer’s: progressive memory loss and neuro-degeneration. The authors suggest that mutations in presenilins could be a cause of Alzheimer’s, mainly due to loss of functionality.

Besides, in this study the researchers identify the molecular mechanisms by which the deactivation of these genes in the mice’s brains leads to memory loss and neuron death. According to this study, the presenilins regulate a group of genes that take part in the process of memory formation. The study suggests that in the first stages of the illness there is a decline in presenilin activity which leads to an imbalance in the cellular processes that control memory and causes neuron death.

The discovery opens new avenues for treatment and prevention of Alzheimer’s disease, a neuro-degenerative disease that affects 400,000 people in Spain, and without any effective treatment. In the opinion of doctor Carlos Saura “pharmacological treatment that activates the cellular pathways regulated by presenilins could prevent or improve memory loss in patients”.

Octavi López Coronado | idw
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