30 March 2015

The 35 million question

Alzheimer's disease

Anna Petrenko, Copper News

When a patient hears the verdict "Alzheimer's disease", the disorders in his brain are at least a decade old. He usually lives only 3-9 years after diagnosis. Early diagnosis of the disease is very little developed, and there are no preventive measures in clinical practice. There are also no medications that could get rid of Alzheimer's disease (AD). Now about 35 million people around the world suffer from it.

The symptoms of the disease are progressive memory loss and a gradual decrease in cognitive functioning (thinking). Disorders occur due to the fact that plaques from beta-amyloid are deposited in the brain, neurofibrillary tangles of abnormal tau protein associated with microtubules are formed. Synaptic connections and nerve cells themselves are lost, especially in the hippocampus and cortex.

Type 3 diabetesThe most common hypothesis of the development of the disease is beta–amyloid.

According to her, beta-amyloid is normally rapidly removed from the brain through the blood-brain barrier (BBB) into the blood. With the disease, the processes slow down, and the protein accumulates between the neurons. And changes in tau protein lead to disruption of intracellular transport. More recently, amyloid accumulations have been found in some people as early as the age of 20.

A new study from the University of Southern California has confirmed the involvement of BBB in the pathogenesis of Alzheimer's disease. Scientists used a new type of MRI to measure the permeability of BBB in young, elderly and people with moderate cognitive impairment – a high risk of developing AD. It turned out that the permeability of the barrier naturally decreases with age and the "garbage" from the brain is not excreted into the blood. In addition, the loss of BBB integrity may play a role in the development of Alzheimer's disease.

About 5% of cases of the disease are genetically determined AD with early onset, which is caused by missense mutations (changes in the nucleotide sequence of DNA) in three genes. For most patients, the disease develops for unknown reasons. For some, the probability of developing AD is initially increased – for example, for women, in the presence of vascular diseases, head injuries, a family history of dementia and some genetic changes. In addition, as many experts now agree, there are also controlled risk factors: depression, diabetes (Alzheimer's disease has even been called "type 3 diabetes"), smoking and obesity in middle age, high blood pressure in middle age, lack of exercise and a lower level of education.

Scientists have even developed a special MIND nutrition plan to prevent AD based on the Mediterranean diet and DASH nutrition for hypertensive patients. It includes 15 product groups. 10 of them are aimed at improving brain health, and it is necessary to monitor the consumption of components from each subsection. These are green leafy and other vegetables, nuts, berries, beans, whole grains, fish, poultry, olive oil and wine. Foods that harm the body are red meat, butter and margarine, cheese, pastries and sweets, fried and fast food.

Disease preventionA clinical diagnosis is usually made on the basis of neuropsychological tests, neuroimaging, analysis of cerebrospinal fluid and blood, but often the disease has already developed strongly at this point.

In addition, some of the tests are invasive and expensive. It is not surprising that in the scientific world so many laboratories are engaged in early diagnosis of AD. Their main goal is to identify the group of patients in whom the disease is likely to develop or has already developed, but there are no clinical symptoms yet.

Researchers from the University of California, San Diego School of Medicine (University of California, San Diego School of Medicine) have discovered a gene and a protein encoded by it that can affect the accumulation of beta-amyloids. Some variants of the SORL1 gene provide some protection against the disease, and others, on the contrary, increase the likelihood of developing AD by 30%.

In the experiment, stem cells were obtained from the skin cells of patients with AD and healthy people, which were differentiated into neurons. In the presence of a protective variant of SORL1 under the influence of the natural brain peptide BDNF (brain-derived neurotrophic factor), the neuron reduced the synthesis of beta-amyloid by about 20%. With an inconspicuous variant, there was no change in production. A third of the U.S. adult population may have an "unprotected" variant of the gene, scientists suggest.

Another group from UPV/EHU – University of the Basque Country (Euskal Herriko Unibertsitatea – Universidad del Pais Vasco University of the Basque Country) is developing a technique for non-invasive diagnosis of AD by the way people speak. This development – Automatic Spontaneous Speech Analysis (ASSA) – allows you to assess the state in a non–stressful environment. A person simply tells something about his life in a relaxed atmosphere, and at this time the program measures certain parameters, for example, the time of pauses that the patient makes, trying to remember the right word.

TreatmentThere are no drugs that could completely cure Alzheimer's disease right now.

However, new techniques are being developed right before our eyes, which may soon enter clinical practice.

For example, a study from Rockefeller University linked AD to chronic inflammation. The disease turned out to be associated with the blood clotting system, which forms blood clots when blood vessels are damaged. Beta-amyloid activates the plasma protein factor XII. Contact activation of this factor triggers a cascade of reactions of the internal hemostasis pathway, which eventually leads to the release of bradykinin, a pro-inflammatory molecule.

When compared with the analyses of healthy people, the level of activation of the contact system was higher in patients with AD. In addition, if beta-amyloid was detected in the cerebrospinal fluid, its concentration correlated with the level of activation of the internal pathway. Scientists suggest that inhibiting this pathway can slow the progression of the disease without increasing the risk of bleeding.

And researchers from the University of Queensland, Australia (and a number of other VM researchers) have proposed a non–invasive ultrasound technology that eliminates beta-amyloid accumulations. Since sound waves gently increase the permeability of the BBB, microglial cells can get into the brain and "clear" it of amyloid plaques. The researchers showed that, according to tests, after such a procedure, 75% of mice have completely restored memory, and there is no harm to brain tissue. The team plans to test the technique on larger animals – sheep, and in 2017 hopes to test it on humans.

Another study involving BBB suggests using magnetic nanoparticles.

Another group from Johns Hopkins University (John Hopkins) found that the elderly with amnesic mild cognitive disorder increased the activity of some areas of the brain, in particular, the hippocampus. Their memory deteriorates more and the risk of developing AD is increased. A study has shown that low doses of the antiepileptic drug levetiracetam reduce hyperactivity of the hippocampus and improve the performance of memory-related tasks. Scientists hope to use the data obtained to prevent progressive decline in cognitive functions and, possibly, AD itself.

The immunological approach was also not left aside: it was proposed to use antibodies against the accumulation of tau protein. It is assumed that such immunotherapy can even reverse, and not only slow down the course of the disease.

Public attentionIn addition to scientific research, social publicity of the problem of the incidence of asthma, various support societies and charitable organizations is also important.

Here it is impossible not to recall the writer Sir Terry Pratchett. The author of more than 70 books, at the turn of the century he was the second most widely read author in the UK – after J.K. Rowling. He has just passed away at the age of 66, eight years after his diagnosis of AD. By his example and active position, he inspired people to live on, despite such a terrible disease.

Portal "Eternal youth" http://vechnayamolodost.ru30.03.2015

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