Possibilities of genetic counseling for Alzheimer's disease

Alzheimer's disease is quite common; it frightens many people due to the peculiarities of its course. In pathology, brain functions are disrupted and nerve cells die. A person’s memory, mental abilities, motor function, and other functions are gradually impaired.

The disease leads to death, and in recent years the person cannot lead a normal life. The patient's relatives may be interested in whether Alzheimer's disease is inherited. To understand the situation, it is important to understand the reasons for its occurrence.

How to diagnose?

There are several methods - from simple to serious laboratory tests. It turns out to be difficult to do this on your own; often people who are fixated on various kinds of illnesses will find an ailment where there is none. To confirm the results, please consult your doctor.

• Tests. There are various questionnaires on the Internet and popular science magazines that allow you to give a subjective assessment of a person’s health from the point of view of the functioning of the central nervous system. The subject is asked to answer questions regarding the state of memory, interpersonal relationships with family, friends and strangers. After working on the questionnaire, you can look at the keys to the test. To ensure the reliability of the result, it is better to consult a doctor who will be able to distinguish true symptoms from fictitious ones;
• Magnetic resonance imaging. Examination of the brain makes it possible to see a complete picture of the functioning of the central nervous system. In addition to this procedure, the doctor prescribes a number of laboratory tests, which together give a holistic picture of the person’s health status.

It is not necessary to wait for obvious symptoms of the disease to appear. If you have any concerns, get examined as soon as possible. It is easier to prevent a disease and delay the onset of negative consequences than to deal with it in the later stages, when medications are powerless.

APOE e4 gene - how to avoid Alzheimer's disease

Even if you carry the APOE e4 gene, the likelihood of developing Alzheimer's disease can be minimized. To do this, it is enough to carry out comprehensive prevention throughout your life, which is generally based on maintaining a healthy lifestyle. Alzheimer's disease, whether hereditary or not, is a danger to anyone. For this reason, doctors recommend that everyone, without exception, take note of the rules developed for APOE e4 carriers.

Methods for reducing the likelihood of developing the syndrome for high-risk groups include: a high level of physical activity, adequate sleep, optimal conditions of the external and internal environment for life.

Methods to reduce the likelihood of developing the syndrome for high-risk groups:

• high level of physical activity – exercise throughout life should be a priority for such people. The types of activities can be very different, the main thing is that they do not deplete the body, but provide a stable load on the heart, blood vessels, and respiratory organs. The preferred areas are running or race walking, swimming, yoga combined with meditation, cyclic sports;
• A properly composed diet means avoiding fatty foods, fried foods, refined sugar, red meat, processed foods, and strong alcohol. The emphasis is on fish, seafood, white meat, fruits, vegetables, slow carbohydrates, and greens. Freshly squeezed juices are of great benefit;
• adherence to a daily routine, proper sleep - lack of sleep, stress, constant changes in schedule negatively affect the general condition of the brain. An adult should sleep 7-8 hours a night, always going to bed at the same time. In this case, daytime rest is contraindicated only if it does not compensate for night wakefulness;
• optimal conditions of the external and internal environment - it is extremely dangerous for people at risk to live in polluted industrial areas. Any inflammatory diseases should be treated immediately to minimize the likelihood of them becoming chronic;
• prevention of TBI - receiving injuries, especially those that lead to loss of consciousness, is unacceptable. Carriers of the APOE e4 gene are not recommended to engage in martial arts or extreme sports;

Stable intellectual stress is another effective method of preventing Alzheimer's disease. Reading, learning foreign languages, solving puzzles, putting together puzzles, and playing music stimulate the formation of connections between neurons. This allows parts of the brain to compensate for each other's functions if necessary.

It is impossible to definitively answer the question of whether Alzheimer's disease is inherited. There is definitely a genetic predisposition to its development. Thanks to modern advances in medicine, even with increased risks, the influence of the hereditary factor can be reduced.

Course of Alzheimer's disease: predementia

The first signs of Alzheimer's disease, which, as mentioned above, are expressed in problems with memory, attention and remembering new information, can take up to 10 years to appear. In medicine they are defined as a state of pre-dementia

This stage of the disease is insidious in that it rarely alarms the sick person’s loved ones. They usually attribute his condition to age, fatigue, workload, etc.

In medicine they are defined as a state of pre-dementia. This stage of the disease is insidious in that it rarely alarms the sick person’s loved ones. They usually attribute his condition to age, fatigue, workload, etc.

Therefore, at this stage of the disease, it is extremely rare to turn to doctors for help, although you should be wary if a loved one is increasingly showing the symptoms described below.

• The patient has problems finding words during a conversation and has difficulty understanding abstract thoughts.
• It is increasingly difficult for such a person to make independent decisions, he is easily lost in a new environment, he loses initiative and the desire to act, and instead appears indifference and apathy.
• The patient has difficulty performing household chores that require mental or physical effort, and gradually loses interest in previously favorite activities.

Gene influence on other types of dementia

Some types of dementia are associated with other genetic defects.

Huntington's disease, for example, changes chromosome 4, which can lead to progressive dementia. Huntington's disease is a dominant genetic disorder. This means that if one parent has the disease, they can pass the gene on to their offspring and they will develop the disease. Symptoms of Huntington's disease usually do not appear until a person is between 30 and 50 years of age. This can make it difficult to predict and diagnose before a person has children and passes on the gene.

Researchers believe that Lewy body dementia or Parkinson's disease dementia may also have a genetic component. However, they also believe that factors other than genetics may play a role in the development of these conditions.

Late stage: severe dementia

The last stage of Alzheimer's disease is manifested by the complete inability of a person to exist without care, since his activity can only be expressed by screams and obsessive movements. The patient does not recognize relatives and friends, is inadequate in the presence of strangers, loses the ability to move and, as a rule, is bedridden.

The patient at this stage is usually not only unable to control the processes of emptying, but even loses swallowing skills.

But the patient dies not from Alzheimer’s disease itself, but from exhaustion, infections or pneumonia that accompany this pathology.

Alzheimer's disease: prevention

Currently, many different options for preventing the disease are proposed, but their effect on its development and severity has not been proven. Studies conducted in different countries and designed to assess the extent to which a particular measure can slow down or prevent the described pathology often give very contradictory results.

However, factors such as a balanced diet, a reduced risk of cardiovascular diseases, and high mental activity can be attributed to those that influence the likelihood of developing Alzheimer's syndrome.

A disease whose prevention and treatment methods have not yet been sufficiently studied, nevertheless, according to many researchers, can be delayed or mitigated by human physical activity. After all, it is known that sports and physical activity have a positive effect not only on waist size or heart function, but also on the ability to concentrate, attentiveness and the ability to remember.

Main symptoms of the disease

This disease was first described by the German psychiatrist Alois Alzheimer back in 1907.

The disease develops gradually, and affected people regretfully note that they have senile insanity. No one notices the progressive development of the problem: neither the affected person nor his relatives. Forgetfulness is an integral part of the life of an elderly person, but it is not always associated specifically with Alzheimer's disease.

Clinical manifestations of Alzheimer's disease progress gradually, slowly growing and increasing in strength, brain cells begin to die in increased volumes. This explains memory loss and the appearance of absent-mindedness and lack of coordination. Over time, the symptoms that appear lead to complete dementia.

At an early stage of development of the disease, the following symptoms are detected:

Alzheimer's disease

1. Changeability in mood, sudden aggression, increased irritability.
2. Decreased motor activity and decreased interest in current events and the world around them.
3. Absence of memories that happened 1 hour ago, yesterday or several years ago.
4. The problem of perceiving a conversation with an interlocutor, the lack of thinking processes and comprehension of what was said or heard, the impossibility of forming an adequate answer to the question posed.
5. Decreased functions of the patient's body.

In most cases, the first signs go unnoticed. They are attributed to the fatigue or inattention of an old person. But negative processes in the head gain momentum during this period.

Strong signs begin to manifest themselves at a time when a significant part of the brain cells are already destroyed. As a result, in addition to the initial symptoms, the following signs may appear:

• Loss of coordination in space and time (disorientation)
• The problem is recognizing familiar and important things
• Depression, uncontrollable anxiety, feeling of fear
• Apathetic mood, complete indifference
• The occurrence of hallucinations, delusional ideas
• Loss of ability to move independently or care for oneself
• Upright walking gives way to a shuffling gait
• Limb spasms may occur (in rare situations)

Symptoms of Alzheimer's disease can be aggravated by the patient being completely alone, abnormal heat or extreme cold in the room where the person lives. Negative processes can be triggered by unfamiliar things or household items, as well as large crowds of both familiar and unfamiliar people.

In addition, the cause of the problem moving from a moderate degree to a more severe one can be stimulated by the uncontrolled administration of medications or the occurrence of an inflammatory process through human infection.

What genes are responsible for the early onset of the disease?

Currently, the APOE gene (located on chromosome 19) is the only identified increased risk gene for AD that can be hereditarily transmitted through the female line to the child. At the molecular level, APOE helps in the synthesis of apolipoprotein E, which is the carrier of cholesterol in the brain. Apolipoproteins are involved in amyloid aggregation and clearance of deposits from the brain parenchyma. When the function of this gene is impaired, excess beta-amyloid deposits occur in the brain, which leads to the development of dementia. There are different forms or alleles of APOE, with the three most common being APOE ε2, APOE ε3 and APOE ε4.

Scientists discover causative genes for Alzheimer's disease

APOE ε2 is rare in the population but may provide some protection against the disease. This allele, as has been shown in studies, can be transmitted through generations (from grandmother to daughter, for example). APOE ε2 transmission reduces the risk of AD incidence to a significant extent.

APOE ε3 is predicted to be the most common allele. However, the APOE ε3 allele does not affect the development of AD.

APOE ε4 is present in approximately 25-30% of the population and 40% of all people with AD. People who develop AD are more likely to have the APOE ε4 allele. APOE ε4 is called a high-risk gene because it increases a person's risk of developing the disease. However, inheriting the A4E4 allele does not mean that a person will definitely develop asthma. Although studies support the association of the APOE ε4 variant and the occurrence of AD, the full mechanism of action and pathophysiology are unknown.

It was also found that the risk of developing the disease is significantly higher in patients with a double variant of the APOEε4 gene than with a single variant. The risk of AD increases 10-fold with double variant APOE ε4 alleles. A stronger correlation is observed in Asian and European patients.

It is unlikely that genetic testing will ever be able to predict the disease with 100% accuracy because so many other factors can influence its development. AD is largely influenced by mental and physical activity. Both factors are almost impossible to predict with high accuracy.

Is heredity always a death sentence?

The discovery of Alzheimer's disease in ancestors or close relatives is not a reason to panic, but a direct indication for seeing a doctor. Even in situations where the probability of developing pathology approaches 100%, timely initiation of prophylaxis can delay the onset of clinical signs. In the case of the polygenic type of syndrome, the chances of a full and long life are very high. This scenario is the most likely. Although it is equated to hereditary, the scenario only affects indicators of potential risks, and does not act as a provocateur of degenerative changes in brain tissue.

The most common and well-studied gene that increases the risk of developing Alzheimer's disease is apolipoprotein, and more specifically, one of its forms, APOE e4. The structural unit is considered relatively “young” and is present in the DNA of 25% of the world's population. Carriage of such a substance leads to early aging of blood vessels, which increases the risk of developing cardiovascular diseases by 40%. It also increases the likelihood of triggering degenerative processes in nerve tissues with their subsequent atrophy. Studies have shown that a person with APOE e4 is 10 times more likely to develop Alzheimer's than someone who is not a carrier. When a person receives a gene from both parents at the same time, the risks increase, but still are not 100%.

Other forms of apolipoprotein also pose a certain degree of danger. One of them is present in double volume in the body of 60% of the planet's population. Only half of its owners develop the syndrome - this happens after the carrier turns 80 years old. Pathology may appear earlier if the rules of prevention are completely ignored.

A small number of people have another form of apolipoprotein, which, on the contrary, protects the brain from degenerative processes. Such groups of people are considered the most protected, but they are also required to follow the rules for preventing the disease.

How is the disease diagnosed?

There is currently no test for Alzheimer's disease that can accurately diagnose it.

Therefore, to clarify the diagnosis, the doctor has to exclude symptoms of other diseases that cause dementia. These may include brain injuries or tumors, infections, and metabolic disorders. These include mental disorders: depression and anxiety syndrome. But even after excluding such pathologies, the diagnosis will be considered only presumptive.

When examining, a neurologist and psychiatrist usually rely on a detailed description by the patient’s relatives of the changes occurring in the patient’s condition. Typically, anxiety symptoms are expressed by repeated questions and stories, the predominance of memories over current events, absent-mindedness, disruption of the usual household chores, changes in personal characteristics, etc.

Photon emission tomography, as well as positron emission tomography of the brain, which makes it possible to recognize amyloid deposits in it, also turns out to be quite informative.

Only a microscopic examination of brain tissue, which is usually carried out posthumously, can confirm the diagnosis absolutely accurately.

When to see a doctor

Seeking medical help for a person who has the symptoms listed above is vital. Your doctor will rule out other conditions that may cause dementia, such as a urinary tract infection or a brain tumor. Before visiting the doctor, family members should make a list of all medications the symptomatic patient is currently taking. Your doctor will review the list to make sure your dementia symptoms are not side effects of your current medications. Keep a diary of noticeable symptoms as they develop to help your doctor identify potential patterns.

Although genetic testing that can help detect genes associated with Alzheimer's disease is available, doctors generally do not recommend this testing for late-onset disease. Having the genes does not necessarily mean that a person will have Alzheimer's disease. Testing may cause unnecessary worry, anxiety and fear. However, a person with a family history of early-onset Alzheimer's disease may wish to undergo genetic testing. Most doctors recommend meeting with a genetic counselor ahead of time to discuss the pros and cons of genetic testing and how they might interpret the results. Sometimes your doctor may recommend genetic testing when early symptoms of Alzheimer's disease appear, as this will help you start treatment earlier.

Genetics and genes

Almost every cell of the human body contains deoxyribonucleic acid (DNA), which is responsible for the human genome. It contains information about the structure, condition of organs and systems, predisposition to diseases and genetically determined pathologies. The hereditary material is represented by 22 pairs of chromosomes (autosomes) and 1 pair of sex chromosomes, which determine the gender of an individual. Genes located on chromosomes characterize hereditary traits transmitted from parent to child.

In scientific practice, there are 2 types of genome differences:

1. Variation is a modification of genes that are passed on to descendants without the presence of anomalies and mutations. They are individual for each person and may include predisposing factors for the development of a certain type of disease, but do not determine it 100%.
2. Mutation is a clear change that occurs over many generations. There is a tendency for different people to develop a specific disease with damage to a precisely defined gene region. An example is inherited dementia due to Huntington's disease.

In discussing whether dementia is inherited or not, the clear answer lies in the fact that genetic etiology is present in any type of dementia. It is the genetic variant of the tendency to heart disease and hemovascular disease (mixed dementia), dysmetabolic processes in the brain (Alzheimer's dementia) and other factors that are transmitted. Even with a threatening risk of developing dementia, the disease may not develop if a correct lifestyle is maintained, a daily routine and rest are observed, and brain function is regularly stimulated.

Determined genes

Researchers have identified three specific deterministic genes that may cause Alzheimer's disease:

1. amyloid precursor protein (APP)
2. presenilin-1 (PS-1)
3. presenilin-2 (PS-2)

These genes are responsible for excessive accumulation of beta-amyloid peptide, a toxic protein that accumulates in the brain. This buildup causes damage and death of nerve cells, which is characteristic of Alzheimer's disease. However, not all people with early-onset Alzheimer's disease have these genes. A person with these genes who develops Alzheimer's disease has a rare type known as familial Alzheimer's disease. Familial Alzheimer's disease accounts for less than 5% of all cases worldwide. Alzheimer's disease, caused by genetic determinants, usually occurs before age 65. Sometimes it can develop in people between 40 and 50 years of age.

Can the disease be inherited?

Doctors, conducting examinations of patients with an identified disease, noticed that such people had relatives with similar signs of the pathological process. Therefore, a large number of research works confirm the proposition that Alzheimer's disease can and is most often transmitted by heredity

High probability of heredity

Moreover, if a disease is detected in one relative in a family, then in the next generation there is a possibility that the disease will manifest itself in much larger quantities. Therefore, all data and examinations carried out during the development of a pathological process in the brain confirm that senile insanity is transmitted at the genetic level.

When a child is formed, a set consisting of 23 chromosomes from the father and mother is incorporated into the structure of its tissues and internal organs. The baby receives all the inclinations and habits from both parents. Under various circumstances, a pathological process develops in which a gene undergoes a mutation procedure.

Those people who are in direct contact with a sick person, be it a parent or sibling, are recommended to undergo an examination and pass a special test for the presence of developing signs of pathology. If you find any results, you should consult a doctor.

To prevent the development of the disease, even if there is a direct relative, it is recommended to carry out a number of preventive measures:

Healthy foods

1. Drive away bad thoughts from yourself, perceive life positively in bright colors.
2. Avoid stressful situations.
3. Protect your own body from the toxic influence of external factors.
4. To refuse from bad habits.
5. Develop intelligence, constantly stimulate brain activity.
6. Eat only proper, balanced foods.
7. Communicate with pleasant and educated people.

There is nothing better for preventing problems than a full life, quality rest, staying with family, loved ones and loved ones.

Forms of predisposition

Based on which chromosome is affected and how many genes are involved in the process, two main forms of predisposition are distinguished. In the first case, only one gene is affected, in the second – several. Each option has its own characteristics, which must be taken into account during diagnosis, prevention, and treatment.

Monogenic

The mutation occurs in one of the genes of the 1st, 14th or 21st chromosomes. The difficulty of making a diagnosis in this case is due to the lack of accurate information among geneticists on all fragments of human DNA. Some of the genes have not yet been identified, which sometimes makes it impossible to identify the pathological link, despite the obvious influence of the hereditary factor.

The difficulty of making a diagnosis in this case is due to the lack of accurate information among geneticists on all fragments of human DNA.

Polygenic

The main mode of transmission of Alzheimer's disease is genetic. If a person’s ancestors have not one altered DNA fragment, but several, then this can manifest itself in a variety of combinations. It is noteworthy that, despite the defeat of several genes at once, the development of senile dementia does not always occur against such a background.

Today, genetics includes two dozen types of gene mutations that can increase the risk of developing Alzheimer's syndrome. In the presence of a hereditary predisposition, the influence of external factors on the body plays an important role.

Pathology of this type usually appears after 65 years, but the first vague signs can be noticed 5-7 years earlier. The more confirmed cases of the disease in a family, the higher the potential risks.

Hypothetical causes of the disease

As mentioned above, heredity only creates a favorable background for the onset and development of pathogenic changes.

What process leads to the death of neurons and the accumulation of plaques? There is no clear answer to this question.

There are three main hypotheses:

• amyloid - the disease occurs due to the deposition of amyloid beta (Aβ);
• cholinergic - due to a decrease in the synthesis of the neurotransmitter acetylcholine;
• tau hypothesis - the process is triggered by deviations in the structure of the tau protein.

The amyloid hypothesis has become most widespread and significant.

Its postulates have been repeatedly proven by its relationship with the genetic model.

Proponents of the concept believe that the accumulation of beta-amyloid consistently triggers the mechanisms of neurodegenerative processes, but does not in itself lead to pathology.

However, the true nature is not clear. It is only clear that years pass from the moment the accumulation begins until the critical point in the death of neurons is reached.

So is Alzheimer's disease inherited or not?

Let's take a closer look at the main features of this disease. Disease

Alzheimer's triggers degenerative processes in the nerve cells of the brain, which causes disruption of the functionality of this organ. The patient's condition will gradually only worsen. At the same time, the negative changes that have occurred will ultimately become irreversible. As a rule, after diagnosis, people live about 7 years, but this is a very average figure. One point should be taken into account. Often several years pass between the appearance of the first signs of the disease and the diagnosis.

If we talk about the heredity factor, then it should be noted that doctors really paid attention to one fact. Most patients diagnosed with Alzheimer's disease had relatives with the same pathology in previous generations

This is also indicated by medical statistics. Accordingly, it should be stated that Alzheimer’s disease is indeed inherited.

As you know, a child receives 23 chromosome pairs from his parents. Each gene contains information about the structure of the human body. Under the influence of certain factors, they can change, that is, mutate. Because of this, a number of pathologies develop, including Alzheimer’s disease. According to scientists, heredity and this disease are closely related.

Moreover, it is now even known which chromosomes are responsible for the development of Alzheimer's disease. These are, in particular:

• first,
• fourteenth,
• nineteenth,
• twenty first.

Both types of pathology can be inherited. In the first, the disease develops at an early age - approximately 30-40 years, while in the second, the pathology appears in much older people. At the same time, scientists argue that the changes that have occurred in the gene structure are far from the only reason for the appearance of this disease in humans. The risk increases significantly in the presence of contributing factors. These, for example, include the environmental situation in the area of ​​residence, as well as a person’s lifestyle.

In other words, the disease can indeed be inherited. However, the presence of a person in the family with Alzheimer’s disease does not mean that the pathology will necessarily appear in a representative of the younger generation. In this case, we need to say that it is not the disease itself that is transmitted. A person inherits only a set of genes that contribute to its development. Moreover, there are 2 types. The first of them provokes the development of the disease at a young age. This genotype is an almost 100 percent guarantee that the disease will be inherited by the younger generation. However, this set of genes is very rare today.

No less important in this aspect is a positive emotional background. It is necessary to avoid stressful conditions as much as possible, learn to think positively and look at life with optimism. Communication with like-minded people can be very useful in this regard. It is also recommended to give up bad habits - smoking, drinking alcohol, drugs. After all, they can also be a factor contributing to the development of the disease. And, of course, don’t forget about the benefits of physical and mental exercise. The main thing is that they are not excessive, since you also need to allocate the appropriate time for rest, otherwise the body will sooner or later fail.

Psychological reasons

A German group of scientists has established a connection between Alzheimer's disease and psychotrauma. Studies have shown that patients with post-traumatic stress disorder (PTSD) and AD patients have reduced levels of FMN2. It is a protein that helps cells maintain their structure and function. As a result of psychotraumatic situations (PTSD), the amount of FMN2 decreases, which causes a disorder in cognitive abilities.

A group of specialists from Göttingen conducted laboratory studies on this theory. In mice with reduced FMN2, symptoms of PTSD and Alzheimer's disease actually increased with age. Such observations made it possible to identify another factor that increases the risk of dementia. Also, tests of some drugs have shown their effectiveness in improving memory in old animals. But the theory of psychological trauma is only one of the factors, but not the root cause of the disease.

Dementia in older people is also considered by psychosomatics. The theories in this area are not taken seriously by most scientists. But since there is no single reason, it makes sense to study all possible aspects. Psychosomatics believes that dementia is an attempt to escape from the world. As dementia progresses, the person truly does not participate in life and cannot take responsibility for themselves or their actions. From this point of view, progressive dementia is the result of great responsibility or unjustified expectations. It is believed that people who criticize themselves and their environment are more susceptible to AD.

One of the authors on the topic of psychosomatic theory, Liz Burbo, put forward her hypothesis about the cause of the disease. Liz is a philosopher and psychologist. She believes that dementia is an attempt to manipulate others and free oneself from any responsibility. The hypothesis may seem true if you look at the patients. They are often irritable, whiny, and unable to do anything themselves. But this is more likely the result of disorders in the brain, and not their cause.

Burbo wrote a book on the psychosomatics of Alzheimer's. It states that AD appears in those who were very active in their youth and tried to remember everything. Such intellectual activity, combined with unjustified hopes, causes dementia. So says Liz and her followers. If you examine the rest of the hypotheses, Bourbo's theory looks like an amateur's guess.

Research shows that an active brain stays healthy longer, and people with non-intellectual jobs are more at risk of AD.

But it has also been proven that severe psychological shocks, depression and frequent neuroses lead to the loss of connections between neurons. Because of this, logical thinking and a sense of reality are reduced.

What therapeutic measures can cure AD in the future?

Effective drugs are being developed to treat Alzheimer's disease

Recent phase 3 immunotherapy studies have shown that an antibody that targets the N-terminal portion of amyloid-β prevents amyloid-β deposition in the brains of APOE ε4 carriers. Bapinezumab also reduces phosphorylated tau levels in the cerebrospinal fluid. Therefore, immunotherapy may be useful in eliminating beta-amyloid from the brains of AD patients.

The main side effects of bapinezumab, namely vasogenic cerebral edema and microhemorrhage, are more common in APOE ε4 carriers. Although bapinezumab failed to prevent cognitive and functional impairment in these clinical trials, combining Aβ immunotherapy and nootropics may lead to improved treatment outcomes.

The presence of a defective allele does not always lead to AD. This genetic isoform likely accelerates the onset and progression of the disease. However, geneticists' understanding of the potential pathogenic link between APOE ε4 and cognitive function may allow early identification of men, women, and children at increased risk of AD.

Hypotheses

The study of the causes of dementia begins at the molecular level. This gives hope to establish a “starting point”, the root cause of the disease. So far, scientists have concluded that AD is a multifactorial disease. In one case it can be caused for one reason, in another - for another. The main hypotheses for Alzheimer's disease include the amyloid, tau, and cholinergic hypotheses.

Cholinergic

All patients with asthma have a reduced level of acetylcholine. It is a neurotransmitter, a microscopic structure that allows electrical impulses to pass between cells in the brain. With acetylcholine deficiency, nerve cells cannot exchange impulses with each other and neighboring tissues. Because of this, motor function, vision, memory, abstract and logical thinking are impaired.

Having discovered this pattern, scientists have created a number of drugs that maintain the desired level of acetylcholine. Symptoms in patients with this therapy become less pronounced, but this does not stop the disease. This means that there are other causes of the disease.

Amyloid

This hypothesis is considered the main one among other assumptions. Even Alois Alzheimer, during the autopsy of his patient with AD, discovered protein deposits in the brain. The study of this phenomenon showed that there are two types of protein that are deposited in brain tissue: amyloid and tau protein. Amyloid is a complex of proteins and polysaccharides; it is involved in metabolism at the cellular level. Normally, this substance is divided into smaller parts and consumed by the body.

With impaired metabolism, amyloid fragments appear that are too long, which do not dissolve and are deposited in the hippocampus and other parts of the brain.

Such accumulations are called plaques. Due to the formation of protein plaques, calcium also accumulates in the brain tissue. This disrupts communication between neurons, and cells that are unable to communicate die. Attempts to correct this situation have so far failed. Even diagnosing plaque accumulation is impossible without an autopsy.

Tau hypothesis

Another type of protein that is deposited in the brain is tau. In a healthy body, it plays an important role as a membrane for living cells. Tau protein is also insoluble, otherwise it would not be able to perform its barrier function. In patients, this component gathers into “balls”, preventing cells from exchanging impulses. The result is the same - the death of neurons and loss of synapses. What exactly leads to disturbances in protein metabolism remains unknown.

Monogenic and polygenic modes of inheritance of Alzheimer's disease

In 80% of all registered cases, the culprit of the monogenic variant of the disease is chromosome 14 (PSEN-1), less often 21 (APP) or 1 (PSEN-2). Alzheimer's disease is inherited through a single mutated gene that is passed on to a child from his parents. The familial form of the disease, which is inherited, usually develops and begins to show noticeable external symptoms at a fairly early age - after 45, and sometimes after 30 years. Experimentally, it was possible to establish that the female body is more vulnerable to the negative effects of hereditary mutations in the APOE chromosome during the period of hormonal fluctuations, while the male brain practically does not react to the genetic defect.

A complex combination of several factors plays a decisive role in whether Alzheimer's disease ultimately turns out to be hereditary or acquired. With a polygenic mode of inheritance, an increased likelihood of triggering destructive processes in the brain is determined by:

• old age;
• poor health;
• wrong lifestyle;
• genetic predisposition.

The interaction of genes with each other and the influence of these factors increase the risk of pathology. At the same time, physical activity, a balanced diet and regular mental training can successfully neutralize the adverse effects of genetics.

Alzheimer's is a hereditary disease, the late onset of which after 65 years of age, and is primarily caused by the apolipoprotein E (APOE) gene.
Structural variations in this gene determine disease rates. Structural variations of apolipoprotein E (APOE)

APOE variant	Person's age (average)	Percentage of total number of patients
e4 not detected	84 years old	20%
One copy of e4	76 years old	47%
Two copies of e4	91 years old	68%

It is impossible to say categorically that Alzheimer's disease is hereditary. In addition to the genetic factor, there are other reasons that can cause irreversible organic changes in the central nervous system. Doctors advise people whose close direct relatives have suffered from senile insanity not to neglect preventive measures and to seek professional medical help at the first signs of cognitive impairment.

Genes affecting the condition and functioning of the brain

The genetic factor underlies many pathologies that are inherited, and dementia is no exception. One of the scientific hypotheses about the possible nature of its origin allows us to make an assumption whether Alzheimer's disease is hereditary. Today, the amyloid theory is fundamental. According to studies, it was possible to establish that the death of nerve cells occurs due to excessive accumulation of dense beta-amyloid plaques in them. The APP gene, which is inherited and located on chromosome 21, is directly involved in the formation of insoluble protein deposits. A mutation of this gene leads to increased production of senile plaques in brain tissue, which interfere with the normal transmission of nerve impulses.

The presence of the APP and APOE4 gene isoforms on chromosome 19 does not mean that Alzheimer's disease will necessarily be inherited from parents to children. Such genetic mutations in the body increase the risk of developing the disease in complex combination with other possible provocateurs of irreversible degenerative changes in the brain. The most common ones include:

• old age after 65 years;
• traumatic brain injuries of the head;
• chronic diseases of the cardiovascular system;
• hormonal imbalances;
• low level of education, low-intellectual occupations;
• prolonged exposure to toxic substances, radiation, electromagnetic radiation;
• alcohol abuse, smoking.

An inherited predisposition to Alzheimer's disease is also observed in people with mutations in the genes of chromosomes 1 and 14, but scientists still find it difficult to name a cause-and-effect relationship between these facts. At present, only the fact has been established that Alzheimer's disease and heredity can be traced in 10% of all registered clinical cases of the disease.

Methods of transmission of the disease

Inheritance of pathology in the first scenario occurs rarely, but in this case the disease develops with 100% probability. Signs usually appear before old age. Persons with this form of predisposition are recommended to undergo special tests at a young age, get advice from a geneticist, and begin intensive prevention.

Heredity according to the first genotype comes in several varieties:

• 1st chromosome - only a few dozen families are at risk. The clinical picture develops quite late;
• 14th chromosome - 400 families with a mutation of this gene are officially registered on the planet. The peculiarity is that against such a background, senile dementia develops very early. Cases of diagnosis at 30 years of age have been reported;
• Chromosome 21 - damage to the gene leads to the development of a pathology called familial Alzheimer's disease. Approximately a thousand families around the world have been diagnosed. The first obvious signs of degenerative changes in the brain are detected at 30-40 years of age.

Chromosome 21 - damage to the gene leads to the development of a pathology, which is called a familial disease, the diagnosis has been made to approximately a thousand families around the world.
Inheritance by the second genotype is diagnosed much more often. It can be triggered by a number of genes, the most well studied of which is apolipoprotein. Its mutation can be detected using special tests, but this approach is still used quite rarely. This type of heredity becomes not the cause of the disease itself, but a predisposition to changes in the structure of the nervous tissue.

Alzheimer's in people with Down syndrome

The inheritance of senile dementia is confirmed by such congenital genomic pathology as Down syndrome. Normally, each person inherits a set of 46 chromosomes from their parents, 23 from the father and 23 from the mother. When the 21st chromosome inherits a third copy instead of one pair, this neurodegenerative syndrome is diagnosed. The assertion that Alzheimer's disease is a hereditary pathology is based on the fact that it is mutations in chromosome 21 that trigger the process of active production of abnormal amyloid plaques in brain cells. Thus, the additional chromosome inherited becomes another source of a protein substance that steadily destroys healthy neurons.

Most people with Down syndrome experience dementia before the age of 40, with an average life expectancy of 50 years. The hereditary predisposition to Alzheimer's disease in individuals with such chromosomal abnormalities provides direct support for the amyloid hypothesis.