Saturday , December 5 2020

Hunt for the hidden footprint of Alzheimer's disease

One of the current problems that has been developing for a long time in the field of public health is the marked tendency to increase the aging population. In America, the forecasts show that by 2025, the number of people over 65 will double, proportionally increasing the issues associated with this stage of life.

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

Taking into account that dementia as a whole and Alzheimer's disease in particular are an epidemic all over the world, the researchers' maximum efforts today are to identify the factors that increase the risk of suffering and act upon them. to prevent them.

The final diagnosis of Alzheimer's disease was confirmed during the study after death, although progress has been made in treatment and early detection in recent years. Finding changes in brain tissue related to early stages of dementia is one of the latest achievements of Pablo Skodeler and Amman Man, conducted at Erkki Rusolati's Lab at the University of California, San Diego, USA.

Scodeller, Mendoza, who studies and earns a doctorate degree in Argentina, tells us about the detection of CTGF (a factor of connective tissue growth factor), a protein that is deposited in the blood vessels in the brain in the early stages of Alzheimer's disease.

"We found that CTGF protein began to accumulate in cerebral blood vessels before the onset of beta-amyloid plaques typical of Alzheimer's disease," Skockler explains. Good tip to unravel this ball

The article published in Nature communication it also describes a short chain of amino acids or peptides called "DAG" that has the property of adhering to CTGF. DAG can be injected into the blood where it quickly seeks out its partner, CTGF.

This is very important for facilitating the diagnosis, as DAG is able to target small pieces of iron oxide, a thousand times smaller than a cell, to the affected area. Accumulation of these particles generates contrast in magnetic resonance tomography, which helps doctors and researchers to find and determine the extent of damage. For Scodeller, DAG can detect Alzheimer's disease much earlier than contrast agents that are currently approved for clinical use.

The DAG peptide may not only be a diagnostic partner but also a therapeutic drug.

"Now you can take CTGF and design some compound that is associated with an important site of this protein and thus remove functionality, or you can create an antibody that blocks it," says Skoderler. "Another therapeutic option would be to prevent the synthesis of CTGF in the two cell types that produce it, the cells of the blood vessels of the brain and the astrocytes, a type of brain cell, although the latter is more difficult to make than the first," he adds.

Another key point of the discovery is that CTGF is exposed in blood vessels, i. E. in contact with the blood so that any therapeutic or diagnostic compound that is injected with blood will have access to it. "It's not that he has to penetrate the tissue or enter the cell that is difficult to achieve in order to reach his goal," Skodeler continues.

Although the study was conducted in models of mice with the disease, the researchers found that DAG binds to CTGF in tissue samples from Alzheimer's disease that is important for translation. "The presence of CTGF at an early stage of the disease opens the door to diagnosis and therapy," says Skodeler, as "CTGF appears in the blood vessels of the brain of Alzheimer's disease long before the metabolic disorders of the brain for the disease."

The Peptide was patented, Scodeller chose Tartu University, Estonia, to continue his research, but San Diego's team continued to work to bring the product to the clinic based on the CTGF targeting concept, as use peptides, small molecules or antibodies, or to improve the diagnosis or to obtain a therapeutic response.

For this, a biotech company (AivoCode, https: / founded a patent license. AivoCode focuses on neurology 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 to the patient and the family and should not leave anyone indifferent.

Risk factors Growing age is one of them, which increases prevalence in an aging society. (AP)

Pathology with enormous social impact

Being the third disease in the cost of social health after ischemic heart disease and cancer, Alzheimer's disease has become an increasingly common disease worldwide. According to official data, today 0.5% of the world's population lives with dementia, which will increase exponentially. About 36 million people suffer from this disease today, a figure that will reach more than 115 million by 2050.

In Argentina, dementia prevalence is generally estimated at 12.2% for those over 65 years of age. According to these figures, we can conclude that there are more than 600,000 dementia in the country, of which approximately 60% are Alzheimer's (360,000 souls). If we add relatives and people dedicated to patient care, the impact on the population is worrying.

Disease also plays a major role in the economy. According to official forecasts, by the end of the year it costs the world billions and will become a trillion dollars.

Observed anomalies in the patient's brain

When observing under a microscope the brain tissue of an Alzheimer's patient, two types of anomalies considered to be characteristic of the disease are evaluated. They are the following:

Amyloid plaques

They are conglomerates of a protein called "beta-amyloid," which damages and destroys neurons in the brain. Although the ultimate cause of neuronal death is unknown, the accumulation of beta-amyloid on the outside of brain cells is the main suspect.


Neurons depend on an internal transport and maintenance system that transports nutrients and other essential materials through 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, which form true tangles in the brain cells, which is why the transport system fails and is another factor contributing to the death of the neurons.

(*) special

(*) neurologist

Print edition

The original text of this article was published on 11/26/2018 in our print edition.

Source link