TO THE HUNTING OF THE HIDEN FOOTPRINT OF THE INCIPIENT ALZHÉIMER

Alzheimer's disease took 20 years of advantage to medical research. This is the time that usually elapses since the neurodegenerative disease begins to develop until the first perceptible symptoms manifest, such as memory loss or disorientation. When neurologists detect Alzheimer's, it has been almost two decades since the brain deterioration really started and little or nothing has to be done: the disease is already at an advanced, irreversible stage, and the only thing to fight it are the symptomatic drugs for slightly improve the condition of the patient.


In recent years, however, the scientific community has stepped on the accelerator and begins to approach positions with the elusive ailment. Researchers seek, against the clock, brain marks and signals that indicate the onset of cognitive decline, before it even causes clinical symptoms. The goal: to tackle and stop the disease in the most incipient stage.

The first alterations produced by Alzheimer's occur at the biochemical level in brain tissue. It involves the accumulation of beta-amyloid (AB) protein plates on the outside of neurons and the intracellular formation of neurofibrillary tangles of TAU protein, the two markers that are shown in the earliest stages of the disease. The presence of amyloid plaques, which are detected through quite invasive techniques such as lumbar puncture or the PET imaging device (positron emission tomography), measures the risk of Alzheimer's disease; The accumulation of TAU threads, which is also determined via lumbar puncture or PET, is a marker of brain damage linked to the death of neurons. The problem is that the accumulation of these proteins is not totally determinant to develop Alzheimer's, as they are also found in other dementias related to aging.

Hence, the next step of the researchers has been to combine the biochemical traces left by the disease with other neuroimaging markers (such as volumetry, measured with an MRI) to fine-tune the early diagnosis of Alzheimer's. In this sense, researchers from the Complutense and Polytechnic universities of Madrid have participated in a study with the National Center for Geriatrics and Gerontology of Japan to detect the first signs of Alzheimer's with minimally invasive markers. The study, published in the scientific journal Brain, found alterations in brain activity patterns related to the amount of amyloid plaques accumulated in the brain.

There are many masked diseases that have the same symptoms as in Alzheimer's. We have analyzed the brain activity of healthy elderly people with mild cognitive impairment through magnetoencephalography (MEG), a technique that detects the magnetic fields generated by the electrical activity of neurons, explains Pablo Cuesta, one of the signatories of the study. . The researchers combined the analysis of the oscillatory patterns of brain activity at rest - in this situation most of the energy emanating from the brain has a frequency of 10 hertz (Hz), 10 waves per second, on which activity oscillates cerebral-with the information collected in the amyloid and glucose PET (to measure neuronal metabolism), and magnetic resonance (estimated damage to brain tissue).

The analysis of brain activity recorded with magnetoeencephalography showed alterations associated with the degree of amyloid beta protein accumulation, the stage of the disease and the level of cognitive impairment, Cuesta says. Scientists already knew that Alzheimer's, like aging, slows the oscillation pattern: the brain emits more energy at low frequencies and less at frequencies close to 10hz. This effect, however, is linked to cognitive impairment, but is not decisive in diagnosing an incipient Alzheimer's. That's why the researchers used the combination of other biomarkers linked to this disease and discovered changes in brain activity associated with people who have amyloid plaques in the brain. "Patients with onset of amyloid accumulation showed an increase in oscillatory activity at 10 hz in the frontal region of the brain compared to subjects without amyloid accumulation," says Cuesta. This marker appeared not only in people with amyloid plaques and mild cognitive impairment, but also in subjects who, despite having amyloid accumulation in the brain, had not yet developed any type of cognitive, structural or metabolic deterioration.

Cuesta argues that the researchers will track the elderly studied to perfect these new biomarkers. The MEG analysis, says the researcher, opens a path to early diagnosis of Alzheimer's with a technically non-invasive.

Without therapeutic alternative

This turn of the screw in Alzheimer's research in favor of the early detection of the disease has, however, left an element in the air: the treatment. In the last 10 years there has been a revolution in the diagnosis of Alzheimer's, but little progress has been made in the treatment. It is frustrating for the patient and for the doctor because you detect it before but you have nothing to give them to stop it, explains Dr. David Pérez, spokesperson for the Behavior and Dementia study group of the Spanish Neurology Society.

There are only symptomatic treatments and the results are poor. "They improve symptoms slightly, but when the patient is already in the dementia phase, he adds. The scientific community investigates molecules to remove amyloid and TAU proteins, but there are still no fruitful results. We are in a stage of reconsideration of what is happening. We do not know the origin of Alzheimer's, what is behind that proteinopathy. There is something hidden that we still do not know, Pérez admits.

Source: El País