In Search of the Hidden Footprint of Alzheimer's Disease

One of the current problems, which has existed for a long time in the field of public health, is the marked tendency to increase the aging of the population. In America, projections indicate that by 2025, the number of people over 65 will double, with a proportional increase in problems badociated with this stage of life.

Our country is in tune with this trend. At the last national census (2010), Argentina had six million adults over 60 years old (14% of the population). This figure puts us in the group of countries with the highest percentage of seniors in the region.

Taking into account that dementia in general, and Alzheimer's disease in particular, is an epidemic worldwide, the maximum effort of researchers today is to determine the factors that increase the risk of dementia. suffer them and act accordingly. to be able to prevent them.

The final diagnosis of Alzheimer's was confirmed during the examination post mortemalthough in recent years, progress has been made in treatment and early detection. One of the recent breakthroughs of Pablo Scodeller and Aman Mann in Erkki Ruoslahti's lab at the University of California at San Diego, USA, was the discovery of changes in brain tissue badociated with the early stages of dementia.

Scodeller, a Mendoza who studied and obtained his doctorate in Argentina, talks about the discovery of CTGF (Connective Tissue Growth Factor), a protein that is deposited in the walls of blood vessels of the brain in the early stages of the disease. # 39; Alzheimer's.

"We discovered that CTGF protein began to accumulate in the cerebral blood vessels even before the appearance of beta-amyloid plaques, typical of Alzheimer's disease," says Scodeller. A good tip to untangle this ball

The article, published in Nature communication it also describes a short chain of amino acids or a peptide, called "DAG", which has the property of sticking to CTGF. DAG can be injected into the blood, where it quickly looks for its partner, CTGF.

This is very important to facilitate diagnosis because DAG is able to direct small iron oxide particles, a thousand times smaller than one cell, to the affected area. The accumulation of these particles generates contrast in magnetic resonance tomography, which helps doctors and researchers locate and define the extent of damage. For Scodeller, DAG could detect Alzheimer's disease much earlier than contrast agents currently approved for clinical use.

The DAG peptide may contain not only a partner for diagnosis, but also a therapeutic drug.

"Now you can take CTGF and design a compound that binds to an important site of that protein to remove the functionality, or you can develop an antibody to block it," says Scodeller. "Another therapeutic option would be to inhibit CTGF synthesis in the two types of cells that produce it, the brain's blood vessel cells and astrocytes, a type of brain cell, although the latter is harder to do than the brain cell. first ", add

Another key element of the discovery is that CTGF is exposed in the blood vessels, ie in contact with the blood, so that any therapeutic or diagnostic compound injected by the blood has access thereto. "It's not that it has to penetrate the tissue or enter the cell, which is hard to reach to reach its target," Scodeller continues.

Although the study was conducted on mouse models with the disease, the researchers found that DAG was related to CTGF in tissue samples taken from patients with Alzheimer's disease, which which is relevant from the point of view of translation. "The presence of CTGF at an early stage of the disease opens the door to diagnosis and treatment," says Scodeller, since "CTGF appears in the blood vessels of the brain of Alzheimer's disease well before the metabolic disorders of the disease. brain for the disease. "

The peptide was patented, Scodeller chose Tartu University, Estonia, to continue his research, but the San Diego team continued their efforts to bring a product to the clinic based on the targeting concept of this target ( CTGF), because either by using peptides, small molecules or antibodies, either to improve the diagnosis or to obtain a therapeutic response.

For this, they founded a biotechnology company (AivoCode, https://aivocode.com), which holds the patent license. AivoCode focuses on neuroscience and is a pioneer in the development of innovative technologies and a broad platform to improve the diagnosis and treatment of neurological diseases.

The results of this study are encouraging. Alzheimer's disease is devastating for the patient and his family and should not leave anyone indifferent.

A pathology with a high social impact

Third disease of the social costs of health after ischemic heart disease and cancer, Alzheimer 's disease has become an increasingly prevalent disease globally. According to official data, 0.5% of the world's population has dementia, a number that will increase exponentially. Some 36 million people suffer from this disease today, a figure that will reach more than 115 million by 2050.

In Argentina, the prevalence of dementia in general is estimated at 12.2% among those over 65 years of age. According to these figures, it can be deduced that there are more than 600,000 people with dementia in the country, about 60% of whom are of the Alzheimer type (360,000 subjects). If we add family members and people dedicated to patient care, the impact on the population is worrying.

The disease also has a significant weight in the economy. According to official forecasts, it will cost the world billions of dollars and will become a disease of one trillion dollars by the end of this year.

Abnormalities observed in the patient's brain

During microscopic observation of the brain tissue of a patient with Alzheimer's disease, two types of abnormalities considered as characteristic of the disease are taken into account. They are:

Amyloid plaques

These are conglomerates of a protein called "beta-amyloid" that damages and destroys brain neurons. Although the final cause of neuron death is not known, accumulation of beta amyloid on the outside of brain cells is the main suspect.

knots

Neurons depend on an internal transport and a support system that carries nutrients and other essential materials throughout their long extensions. This system requires the structure and normal functioning of a protein called "Tau".

In Alzheimer's disease, the threads of the Tau protein are twisted, forming true tangles in brain cells. This is why the transport system is failing and is another contributing factor to the death of neurons.

(*) Special

(*) neuroscientist