Causes of Alzheimer's disease

Alzheimer's disease is considered the most common type of age-related dementia: this pathology occurs in approximately 40% of cases of all diagnosed dementias. A hundred years ago, the disease was considered very rare. However, today the number of patients is growing rapidly: so much so that the disease is already classified as an epidemic pathology. And the worst thing is that the exact causes of Alzheimer's disease have not yet been determined. Doctors are sounding the 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.

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Causes of Alzheimer's Disease

The reasons for the development of such a disease as Alzheimer's disease have not been fully clarified by scientists to this day. Several assumptions have been presented that could explain the emergence and further aggravation of degenerative reactions in the central nervous system. But: none of the existing assumptions are recognized by the scientific community.

The disturbances in the brain that accompany Alzheimer's disease are detected during diagnosis: however, no one has yet been able to determine the mechanisms of the origin and progression of atrophy of brain structures.

Experts admit that Alzheimer's disease has not one, but at least several causes. Genetic defects play the main role in its development: this is especially true for rare types of the disease that begin to develop at a relatively early age (before 65 years).

Hereditary Alzheimer's disease is transmitted in an autosomal dominant manner. With this type of transmission, the probability of the disease appearing in a child is equal to 50%, less often – 100%.

Quite recently, scientists were able to identify three pathogenic genes that act as provocateurs in the development of early senile dementia. Most often, Alzheimer's disease is diagnosed, provoked by a change in the gene located on chromosome XIV. Such a defect occurs in approximately 65% of patients with this disease.

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

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Theories of development

Over the past few decades, scientists have conducted a lot of research into the causes of Alzheimer's disease. However, the exact cause of the disease remains unclear. Today, specialists have a considerable 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 caused by heredity, and in others - by other reasons. It is also generally accepted that the early development of the disease (before the age of 65) is predominantly related to the hereditary type. However, such hereditary early variants are only 10% of the total number of people who fall ill.

Not long ago, scientists conducted another study, 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 the disease is estimated at 100%.

But even the colossal breakthrough of scientists in the field of molecular genetics could not answer the question of the development of Alzheimer's disease in the majority of patients.

What theories do scientists propose to answer the question of the causes of Alzheimer's disease? There are more than a dozen such theories, but three of them are considered leading.

The first theory is “cholinergic”. It is the basis for most of the treatment methods used for Alzheimer’s disease. According to this assumption, the disease develops due to decreased production of such a neurotransmitter as acetylcholine. Recently, this hypothesis has received a large number of refutations, and the most important of them is that drugs that correct the lack of acetylcholine are not particularly effective in Alzheimer’s disease. Presumably, other cholinergic processes take place in the body – for example, the launch of full-length amyloid aggregation, and, as a result, generalized neuroinflammation.

Almost thirty years ago, scientists proposed a second potential theory, called the “amyloid” theory. According to this hypothesis, the primary cause of Alzheimer’s disease is the accumulation of β-amyloid. The information carrier encoding the protein that serves as the basis for the formation of β-amyloid is localized in chromosome 21. What indicates the reliability of this theory? First of all, the fact that all individuals with an additional chromosome 21 (Down syndrome) have a pathology similar to Alzheimer’s disease upon reaching the age of 40. Among other things, APOE4 (the basic factor of the disease) provokes excessive accumulation of amyloid in brain tissue before clinical signs of the disease are detected. Even during experiments on transgenic rodents in which a mutated type of the APP gene was synthesized, fibrillar accumulations of amyloid were observed in their brain structures. In addition, rodents were observed to exhibit other painful symptoms characteristic of Alzheimer's disease.

Scientists have managed to create a specific serum that cleanses brain structures from amyloid deposits. However, its use did not have a pronounced effect on the course of Alzheimer's disease.

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

Spiritual Causes of Alzheimer's Disease

Some experts suggest that Alzheimer's disease is the result of the deposition of amyloid protein substances in the places where neurons connect - inside synapses. Protein substances form a certain type of connection with other substances, which seems to connect the inside of neurons and their branches. This process is detrimental to the normal functioning of cells: the neuron loses the ability to receive and transmit impulses.

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

Alzheimer's disease always appears in the second half of life: this may mean that the connection with oneself is lost, or is transferred to the physical level. Patients literally "fall into childhood", and obvious degradation is noted.

Growing interruptions affecting short-term memory indicate a separation from responsibility for what is in the immediate environment. A person who does not remember and lives outside of reality cannot initially be responsible for anything. The discord in the memorization processes leads to the patient living only in the present moment, or he manages to connect the past and the present. Living in the "here and now" type can become an insoluble problem, and even frightening. The same can be said about the gradual loss of orientation. A person realizes that he has not yet achieved the true goal in life, but the road along which he should move is lost. He loses reference points for his location, does not know where his path leads. Since the traveler does not see the light along his path, he also loses hope.

The result is repeated and prolonged depression and loss of faith in the future.

Since self-control also gradually comes to naught, patients may experience spontaneous emotional outbursts – like a small child, for example. All the educational moments developed throughout life are destroyed. At night, such a person may wake up in the dark, screaming that he does not know his name and whereabouts.

Loss of speech skills may indicate a lack of desire to speak – after all, the world does not evoke any feelings in the patient other than bewilderment.

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

Since Alzheimer's disease potentiates age-related degradation phenomena, it shows the general state of society, which "gives out" an increasing number of patients with this disease. Such a probable cause of Alzheimer's disease as calcification can affect almost all vessels. Protein deposits are formed much earlier than calcareous, cholesterol or lipid deposits, so 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 Alzheimer's patients are predisposed to death within three years of the onset of the disease. In terms of mortality rate, Alzheimer's disease is in 4th place, after heart attack, stroke and oncology.

Alzheimer's disease begins gradually, almost unnoticeably: patients themselves note a constant feeling of fatigue and slowing of brain activity. The first signs appear at about 60-65 years of age, gradually increasing and worsening.

The cause of death in Alzheimer's disease in the vast majority of cases is the failure of the nerve centers in the brain - those centers that are responsible for the functioning of vital organs. For example, the patient may develop severe dysfunctions of the digestive system, lose the so-called muscle memory, which is responsible for the heartbeat and lung function. As a result, cardiac arrest occurs, or congestive pneumonia develops, or other life-threatening complications arise.

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Pathogenesis of Alzheimer's disease

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

The following factors can be considered completely irreparable:

• old age (according to statistics, in those over 90 years old, Alzheimer's disease is detected in more than 40% of cases);
• belonging to the female gender;
• previous traumatic brain injuries, which include damage to the skull during childbirth;
• severe stress;
• frequent or prolonged depression;
• poor intellectual development (eg, lack of education );
• low 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 a state of prolonged hypoxia.

A person can reduce the risk of developing Alzheimer's disease if he or she eliminates the most common risk factors:

• overweight;
• physical inactivity;
• excessive caffeine intake;
• smoking;
• low mental activity.

Sadly, there is a proven fact: ignorance and narrow-mindedness can directly influence the development of the disease. Low intelligence, poor speech, narrow outlook - these 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, loss of nerve cells is observed, synaptic connections in the cortex of the hemispheres and in individual subcortical zones are disrupted. When neurons die, damaged zones atrophy, degenerative processes are observed affecting the temporal and parietal lobes, the area of the frontal part of the cingulate cortex and the cingulate gyrus.

Amyloid deposits and neurofibrillary tangles can be seen under a microscope during a postmortem examination. The deposits appear as condensations of amyloid and cellular elements within and on the surface of neurons. They enlarge in the cells to form fibrous, dense structures sometimes called tangles. Older people often have these deposits in their brains, but patients with Alzheimer's disease have especially large numbers of them, often in specific areas of the brain (such as the temporal lobes).

• Biochemical characteristics of Alzheimer's disease.

Scientists have established that Alzheimer's disease is a proteinopathy - a pathology related to the accumulation of abnormally structured proteins in brain structures, including β-amyloid and tau protein. The accumulations are formed by small peptides 39-43 amino acids long: they are called β-amyloids. They are parts of the precursor protein APP - a transmembrane protein involved in the development and regeneration of nerve cells. In patients with Alzheimer's disease, APP undergoes proteolysis through mechanisms that are still unclear, dividing into peptides. The strands of β-amyloid formed by the peptide stick together between cells, forming compactions - the so-called senile plaques.

According to another classification, Alzheimer's disease also represents a class of tauopathies - diseases related to incorrect, abnormal aggregation of tau protein. Each nerve cell has a cellular skeleton, partially consisting of microtubes. These tubes act as a kind of guide for nutrients and other substances: they connect the center of the cell with its periphery. Tau protein, together with some other proteins, maintains a connection 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 production and further accumulation of amyloid peptides leads to pathological changes characteristic of Alzheimer's disease. The accumulation of amyloid was positioned as the main link in the degenerative process of nerve cells. Perhaps, the accumulations interfere with the homeostasis of calcium ions, which leads to apoptosis. At the same time, it was discovered that amyloid accumulates in mitochondria, blocking the function of individual enzymes.

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

• Genetic features of Alzheimer's disease.

Three genes responsible for the early development of Alzheimer's disease (before age 65) have been identified. The key role is given to APOE, although not all cases of the disease are associated with this gene.

Less than 10% of early-onset diseases are related to familial mutations. Changes have been found in the genes APP, PSEN1 and PSEN2, which primarily speed up the release of a small protein called abeta42, the main ingredient in amyloid deposits.

The detected genes do not indicate predisposition, but partially increase the risk. The most common genetic factor is considered to be the familial allele E4, related to the APOE gene. Almost 50% of cases of the disease development are associated with it.

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