Causes of Alzheimer's Disease

Alzheimer's disease is considered the most common type of age-related dementia: this pathology occurs in about 40% of all diagnosed dementias. A hundred years ago, the disease was considered very rare. However, to date, the number of patients is growing rapidly: so much so that the disease is already classed as epidemic pathologies. And, the most terrible thing is that the exact causes of Alzheimer's disease have not yet been clarified. Doctors sound alarm, since the lack of sufficient information about the causes does not make it possible to stop the development of the disease, which often leads to the death of patients.

[1], [2], [3], [4], [5]

Causes of Alzheimer's Disease

The causes of the development of such a disease as Alzheimer's disease, until today, scientists have not fully figured out. There are several assumptions that could explain the appearance and further aggravation of degenerative reactions in the central nervous system. But: none of the available assumptions is recognized by the scientific community.

Violations in the brain that accompany Alzheimer's disease are found during the diagnosis: the mechanisms of nucleation and flow of brain structures atrophy have not yet been found out by anyone.

Specialists recognize that Alzheimer's disease has not one, but at least several causes of appearance. The main role in development is played by genetic malfunctions: especially it concerns rare varieties of the disease, which begin their formation at a relatively early age (up to 65 years).

Hereditary Alzheimer's disease passes through an autosomal dominant variant. With this method of transition, the probability of the occurrence of the disease in a child is equal to 50%, less often - 100%.

More recently, scientists have been able to determine the top three pathogenic genes that act as provocateurs in the appearance of early senile dementia. Most often, Alzheimer's disease is diagnosed, provoked by a change in the gene that is on the XIV chromosome. A similar defect occurs in about 65% of patients with this disease.

Approximately 4% of cases of hereditary Alzheimer's disease is associated with an impaired gene in the I chromosome. With such a defect, the disease does not always develop, but only if there are certain risk factors.

[6], [7]

Theories of development

Over the past few decades, scientists have done a lot of research on the causes of Alzheimer's disease. Nevertheless, the exact cause of the disease remains unclarified. To date, specialists have a fair list of theoretical assumptions that could explain why Alzheimer's disease occurs. There is clear evidence that the pathology has a heterogeneous origin - that is, in some patients it is due to heredity, and in others - to other causes. It is also believed that the earlier development of the disease (up to the age of 65) predominantly belongs to the hereditary type. However, such hereditary early variants are only 10% of the total number of people who fell ill.

Not so long ago, scientists conducted regular studies, during which they managed to identify three genes responsible for the hereditary tendency of Alzheimer's disease. If a person has this combination of genes, then the risk of developing a disease in him is estimated at 100%.

But even the colossal breakthrough of scientists in the field of molecular genetics could not give an answer to the question of the development of Alzheimer's disease in the prevailing number of patients.

What theories are suggested by scientists to answer the question about the causes of Alzheimer's disease? Such theories are known for more than a dozen, however, three of them are considered to be the leading ones.

The first theory is "cholinergic". It was she who formed the basis of most of the treatment methods used in Alzheimer's disease. If you believe this assumption, the disease develops due to a lower output of such a neurotransmitter, as acetylcholine. Recently, this hypothesis has received a large number of denials, and the most important of them is that drugs correcting the shortage of acetylcholine are not particularly effective in Alzheimer's disease. Presumably, other cholinergic processes take place in the body - for example, the triggering of full amyloid aggregation, and, as a consequence, generalized neuroinflammation.

Almost thirty years ago, scientists proposed a second potential theory, called "amyloid." If you believe this assumption, then the root cause of Alzheimer's disease lies in the accumulation of β-amyloid. The information carrier encoding the protein serving as the basis for the formation of β-amyloid is located on chromosome 21. What does this theory indicate? First and foremost, the fact that all individuals with an additional chromosome 21 (Down's syndrome) after reaching the age of 40 have a pathology similar to Alzheimer's. Among other things, APOE4 (the underlying factor of the disease) provokes excessive accumulation of amyloid in the brain tissues until the clinical signs of the disease are detected. Even during experiments on transgenic rodents, in which the mutated type of the APP gene was synthesized, retention of fibrillar accumulations of amyloid was observed in their brain structures. In addition, rodents also noticed other painful symptoms, characteristic of Alzheimer's disease.

Scientists managed to create a specific serum, cleansing the brain structures from accumulations of amyloid. However, its use had no significant effect on the course of Alzheimer's disease.

The third basic hypothesis was the tau theory. If you believe this assumption, a series of disorders in Alzheimer's disease begins with a structural breakdown of tau protein (protein tau, MAPT, tau protein). As scientists have suggested, the strands of maximally phosphorylated tau-protein are connected with each other. As a result, neurofibrillary glomeruli are formed in the neurons, which leads to a disruption in the integration of microtubules and the failure of the intraniral transport mechanism. These processes provoke a change in the biochemical signaling of the intercellular communication, and subsequently lead to cell death.

The spiritual causes of Alzheimer's disease

As some experts suggest, Alzheimer's disease is the result of the deposition of amyloid protein substances at the junction of neurons - inside the synapses. Protein substances form with other substances a certain kind of compound that, as it were, binds the inner part of neurons and their branches. Such a process is disastrous for the normal functioning of cells: the neuron loses its ability to receive and transmit impulses.

According to the assumptions of individual experts who are engaged in spiritual practice, the connection between macromolecules is inhibited at the stage between the brain department, which is responsible for the logic, and the lymphatic system. Simultaneously with the loss of memory, intelligence, orientation and ability to talk, a person retains social adaptation, musical ear and ability to feel.

Alzheimer's disease always appears in the second half of the life path: it can mean that the relationship with oneself is lost, or it is transferred to the physical stage. Patients literally "fall into childhood", there is obvious degradation.

The growing interruptions affecting short-term memory indicate a separation from responsibility for what is in the immediate environment. A person who does not understand and dwells outside reality, initially can not be responsible for anything. Discord in the processes of memorization leads to the fact that the patient lives only at the present moment, or he manages to connect the past and the present. Living like "here and now" can become an insoluble problem, and even scary. The same can be said about the gradual loss of orientation. A person realizes that he has not yet reached the real goal in life, but the road by which he should move is lost. He loses the landmarks of his location, does not know where his path leads. Since the traveler does not see light in the course of his direction, he loses hope.

As a result, repeated and prolonged depression, loss of faith in the future.

Since self-control also gradually goes to "no", patients can experience spontaneous emotional outbursts - for example, like a small child. All the educational moments worked out in life are destroyed. At night, such a person can wake up in the dark, shouting that he does not know his name and location.

Loss of speech skills may indicate a lack of desire to speak - because the world does not cause any other feelings in the patient, except bewilderment.

Depression often indicates a relaxation, a call to the past and a real state of mind. A patient with Alzheimer's disease can create a sense of euphoria and stay in it for a long time.

Since Alzheimer's disease potentiates the age-related phenomena of degradation, it shows the general state of society, which "gives" an increasing number of patients with this disease. This probable cause of Alzheimer's disease, like calcification, can affect almost all the vessels. Protein accumulation is formed much earlier than calcareous, cholesterol or lipid deposits, therefore it is necessary to direct all attention to this factor, many experts believe.

Causes of death in Alzheimer's disease

According to the latest statistics, approximately 60% of patients with Alzheimer's disease have a predisposition to death in the course of three years from the onset of the disease. According to the percentage of mortality, Alzheimer's disease is on the 4th place, after a heart attack, stroke and oncology.

Alzheimer's disease begins gradually, almost imperceptibly: the patients themselves note a constant feeling of fatigue and a slowing of brain activity. The first signs are manifested approximately from 60-65 years, gradually increasing and aggravating.

The cause of death in Alzheimer's disease in most cases is the failure of nerve centers in the brain - those centers that are responsible for the work of vital organs. For example, a patient can develop severe dysfunction of the digestive system, lose the so-called muscle memory, which is responsible for the heartbeat and lung function. As a result, cardiac arrest stops, or stagnant pneumonia develops, or other deadly complications arise.

[8], [9], [10], [11], [12], [13]

Pathogenesis of Alzheimer's disease

As we noted earlier, scientists do not have accurate, verified data on the true causes of Alzheimer's disease. However, the fact that the rapid development of the disease occurs in old age can be considered already as a certain dependence on age. Age-related changes can be considered a major risk factor for Alzheimer's disease.

To completely incorrigible factors are:

• senile age (according to statistics, those who are more than 90 years old, Alzheimer's disease is detected in more than 40% of cases);
• belonging to the female sex;
• previously suffered craniocerebral injuries, which include and damage to the skull during childbirth;
• severe stress;
• frequent or prolonged depression;
• weak intellectual development (for example, lack of education );
• little mental activity throughout life.

Theoretically correctable factors include:

• excessive pressure on blood vessels due to hypertension and / or atherosclerosis;
• hyperlipidemia;
• high blood sugar, diabetes;
• respiratory or coronary diseases that contribute to the state of prolonged hypoxia.

A person can lower the risk of developing Alzheimer's disease if he also eliminates the most common risk factors:

• overweight;
• hypodynamia;
• excessive passion for caffeine;
• smoking;
• little mental activity.

It is sad, but there is a confirmed fact: lack of education and narrow thinking can directly influence the development of the disease. Low level of intelligence, low-literacy speech, narrow horizons are also probable causes of Alzheimer's disease.

Pathogenetic characteristics of Alzheimer's disease

• Neuropathological features of Alzheimer's disease.

With the onset of the disease, there is a loss of nerve cells, a synaptic connection is broken in the cerebral cortex and in certain subcortical zones. With the death of neurons, the damaged zones become atrophied, degenerative processes affecting the temporal and parietal lobe, the region of the frontal lobar cortex and the cingular gyrus are observed.

Amyloid accumulations and neurofibrillary glomeruli can be examined with a microscope during pathoanatomical examination. Clusters are found in the form of amyloid seals and cellular elements in the neurons themselves and on their surface. In cells, they increase, forming fibrous dense structures, which are sometimes referred to as glomeruli. Old people often have clots in the brain, but in patients with Alzheimer's disease, they are especially numerous, and in separate brain areas (for example, in the temporal lobes).

• Biochemical characteristics of Alzheimer's disease.

Scientists have established that Alzheimer's disease refers to proteinopathies - pathologies related to the accumulation in the brain structures of abnormally structured proteins, which include β-amyloid and tau protein. Clusters are formed by small peptides of 39-43 amino acids in length: they are called β-amyloids. They are parts of the precursor protein APP, a transmembrane protein that takes part in the development and regeneration of the nerve cell. In patients with Alzheimer's disease, the process of proteolysis, with division into peptides, has not been clarified until now with APP. The β-amyloid strands formed by the peptide are glued between the cells, forming seals - the so-called senile plaques (amyloid plaques).

According to another classification, Alzheimer's disease is also a class of taupaties - diseases related to abnormal, anomalous aggregation of tau protein. Each nerve cell has a cellular skeleton, partly consisting of microtubules. These tubes play the role of a kind of guide for nutrients and other substances: they connect the center of the cell with its periphery. Tau protein, in combination with some other proteins, maintains contact with microtubes - for example, it is their stabilizer after the phosphorylation reaction. Alzheimer's disease is characterized by excessive, maximum phosphorylation, which leads to the gluing of protein strands. In turn, this disrupts the transport mechanism in the nerve cell.

• Pathological characteristics of Alzheimer's disease.

There is no data on how the mechanism of disruption of the production and further accumulation of amyloid peptides leads to pathological changes characteristic of Alzheimer's disease. Accumulation of amyloid was positioned as the main link in the degenerative process of nerve cells. Perhaps the clusters interfere with the homeostasis of calcium ions, which leads to apoptosis. It was found that the amyloid accumulates in the mitochondria, blocking the function of individual enzymes.

Probably, inflammatory reactions and cytokines are of considerable pathophysiological importance. The inflammatory process is accompanied by imminent tissue damage, but in the course of Alzheimer's disease it plays a secondary role, or is an indicator of the immune response.

• Genetic features of Alzheimer's disease.

A triple of genes responsible for the earlier development of Alzheimer's disease (up to the age of 65) is isolated. In this case the basic role is assigned to APOE, although not all cases are associated with this gene.

Less than 10% of early diseases are related to family mutations. The changes were found in the APP, PSEN1 and PSEN2 genes, which primarily accelerate the release of the small protein abeta42, the main ingredient in amyloid accumulations.

Discovered genes do not mean predisposition, but partially increase the risk. The most common genetic factor is the family allele E4, which belongs to the APOE gene. With her, almost 50% of the episodes of the disease develop.

Scientists unanimously believe that other genes, with varying degrees of likelihood, are related to the occurrence of Alzheimer's disease. At the moment, experts have analyzed about four hundred genes. For example, one of the detected variations of RELN is implicated in the development of Alzheimer's disease in female patients.