Possible origin of the “toxic cascade” that triggers Alzheimer’s discovered

The laboratory of the researcher from the Neurosciences Institute, the joint centre of the Miguel Hernández University (UMH) and the National Scientific Research Council, Javier Sáez Valero, has published the results of research that points to the possible triggering mechanism for Alzheimer’s. The results of this research could be applied, in the short term, to improving the diagnostic method and, in the future, to intervening therapeutically in the advance of this neurodegenerative disease, which is only diagnosed in 1 out of every 4 cases.

According to the team of UMH researchers, despite important advances in research made over recent years, the causes and development of Alzheimer’s disease remain unclear. One of the key questions is deciphering why the production of beta amyloid, the protein that causes the “toxic cascade” that triggers the disease, increases in the brains of people with Alzheimer’s.

In the laboratory of Professor Sáez Valero, they have discovered that the glycosylation of the amyloid precursor in the brains of patients with Alzheimer’s is altered and is probably therefore processed differently than in a healthy brain. The researchers believe that this phenomenon is what triggers the pathology.

The glycosylation is the process whereby carbohydrates are added to a protein. This process determines the fate of proteins to which a chain of glucides (glycoproteins) has been added, which will mostly be secreted or will form part of the cell surface, as in the case of the Amyloid Precursor Protein (APP). Alteration of this glycosylation process is the origin of various pathologies.


This new finding opens up the possibility, in the short term, of finding a good biomarker for diagnosis, through the analysis of the glycosylation of the beta-amyloid fragments and, in the longer term, for therapeutic intervention


This new finding of the UMH researchers, which has been published in the Alzheimer´s Research & Therapy magazine, opens up the possibility, in the short term, of finding a good biomarker for diagnosis, through the analysis of the glycosylation of the beta-amyloid fragments and, in the longer term, for therapeutic intervention. This work was carried out in brain samples postmortem and in cell cultures. The next step in the research will be the analysis of APP fragments in the cerebrospinal liquid, focusing on their glycosylation.

VÍDEO: Nueva alteracion en el cerebro de las personas con Alzheimer

According to Professor Javier Sáez Valero, head of the UMH’s ‘Altered molecular mechanisms in Alzheimer’s disease and other dementias’ research group, this is an encouraging finding during this Alzheimer’s month. The 21st September is the world day for this disease for which there is still no treatment, which affects 1,2000,000 people in Spain and whose incidence will triple over the next few decades. A harsh reality, which has grown worse with the current Covid-19 pandemic, due to lockdown, which has caused an even quicker decline in the cognitive abilities of those affected, according to a declaration by Alzheimer Europe.

According to data from the Spanish Neurological Society, around 40,000 new cases of Alzheimer’s, a disease associated with age that affects one out of every 10 people over the age of 65 and one out of every 3 over 85, are diagnosed each year. Notwithstanding, it is estimated that 80% of mild Alzheimer’s cases are undiagnosed and between 30 and 40% of total cases also go undetected.

Professor Sáez Valero focused his research on Alzheimer’s diseases, with approaches ranging from therapy to diagnosis. He is also part of the research institute network that coordinates basic and clinical research groups with an interest in neurodegenerative diseases such as Alzheimer’s (CIBERNED).


Source: https://comunicacion.umh.es
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