Recent studies about Alzheimer’s disease in the world

Recent studies about Alzheimer’s disease in the world: a deep analysis of progress and challenges

I. Pathogenesis and molecular mechanisms:

1. Amyloid hypothesis: revaluation and new directions. The amyloid plaque, formed by the aggregates of the beta-amyloid (Aβ), is traditionally considered the central link in the pathogenesis of Alzheimer’s disease (BA). However, recent studies show that the role of Aβ can be more complex and multifaceted than previously considered. Some studies indicate that it is not the plaques themselves, but the soluble Aries oligomers have the greatest neurotoxicity. The focus shifts the study of the mechanisms by which the Aries oligomers cause synaptic dysfunction, impaired ion transport and the activation of inflammatory processes. In addition, various forms of Aβ, such as Aβ40 and Aβ42, and their relative effect on the development of BA are investigated. Genetic studies have identified mutations in the App, Psen1 and Psen2 genes, which lead to increased Aβ products, confirming the relationship between Aβ and hereditary forms of BA. However, not all people with a high level of Aβ develop BA, which indicates the role of other factors, such as tau-pathology, inflammation and genetic predisposition. Actual studies study the interaction of Aβ with other proteins and cellular components, and also develop new therapeutic strategies aimed at preventing the formation of Aβ oligomers or their neutralization. For example, antibodies specific to various forms of Aβ oligomers are developed, in order to selective targeting the most toxic protein forms.

2. Tau-pathology: role in the progression of the disease. Hyperfosporized tau-prothein forms neurofibrillar balls (NFK), which are another key sign of BA. Unlike Aβ, the spread of the NFC correlates well with cognitive deterioration. Studies show that tau-pathology can be caused by Aβ, but it can also spread independently, acting as a “aus-like” protein. The phosphorylation of Tau Protein leads to its separation from microtubules, which violates the transport of substances inside neurons and leads to their death. Actual research is aimed at studying the mechanisms that regulate the phosphorylation and aggregation of Tau Protein, as well as the development of therapeutic strategies aimed at preventing the formation of NFC or removing them. For example, kinaz inhibitors are developed involved in the phosphorylation of the Tau, as well as antibodies specific to various forms of phosphorized tau. The role of microglia and astrocytes in the spread of Tau-pathology is also studied.

3. Inflammation and immune dysfunction. Chronic inflammation in the brain plays an important role in the development and progression of BA. Activated microglia and astrocytes release pro -inflammatory cytokines and chemokins, which contribute to neurodegeneration. Genetic studies have revealed variants of genes associated with the immune system that increase the risk of BA. For example, the Trem2 gene option, which is expressed in microlytes, is associated with an increased risk of BA. Trem2 plays a role in phagocytosis of Aβ and other cell fragments, and its dysfunction can lead to the accumulation of Aβ and increased inflammation. Actual studies study the interaction between Aβ, Tau-pathology and inflammation, and also develop therapeutic strategies aimed at modulating the immune response in the brain. For example, anti -inflammatory drugs, as well as therapeutic approaches aimed at activating microglia for phagocytosis Aux and Tau are investigated.

4. Synaptic dysfunction and loss of neurons. Sinaptic dysfunction is an early sign of BA and correlates well with cognitive deterioration. Aux oligomers and tau-pathology disrupt the synaptic transmission, which leads to the loss of synapses and neurons. Actual studies study the mechanisms by which Aβ and Tau violate the synaptic function, and also develop therapeutic strategies aimed at protecting synapses and the restoration of synaptic transmission. For example, preparations that enhance neurotransmission, as well as therapeutic approaches aimed at stimulating neurogenesis, are investigated. The role of various types of neurons and their vulnerability to Aβ and Tau are studied. The role of neurotrophic factors, such as BDNF, is also investigated in maintaining synaptic function and neuronal survival.

5. Genetic risk factors and protective genes. Genetics plays an important role in the development of BA. Mutations in the App, Psen1 and Psen2 genes lead to the early development of hereditary BA. However, most cases of BA are sporadic and are associated with the interaction of genetic and environmental factors. Apopolipoprotein E (APOE) is the main genetic risk factor for sporadic BA. The APOE4 option is associated with an increased risk of BA, and the APOE2 option is reduced with a reduced risk. APOE plays a role in the transport of lipids and cholesterol in the brain, as well as in the clearance of Aux. Actual studies study the mechanisms by which APOE affects the risk of BA, and also develop therapeutic strategies aimed at modulating APOE activity. Other genes that can affect the risk of BA, such as CLU, CR1 and Picalm are identified. The study of these genes can help in the development of new therapeutic goals.

6. Vascular factors and cerebrovascular diseases. Vascular factors, such as arterial hypertension, diabetes and atherosclerosis, increase the risk of BA. Cerebrovascular diseases, such as strokes and microinfarcts, can aggravate cognitive deterioration in BA. Actual studies study the interaction between vascular factors, Aβ and Tau-pathology. For example, vascular factors can lead to a violation of the Aβ clearance from the brain, which contributes to its accumulation. The role of inflammation and endothelial dysfunction in the development of vascular diseases and BA is also studied. Preventive measures aimed at monitoring vascular risk factors can help reduce the risk of BA.

7. Violation of brain metabolism and energy deficiency. With BA, there is a decrease in glucose metabolism in the brain, especially in the temporal and parietal areas. This can lead to energy deficiency and impaired neuron function. Actual studies study the mechanisms by which Aβ and Tau disrupt glucose metabolism, and also develop therapeutic strategies aimed at improving the metabolism of the brain. For example, drugs that improve the function of mitochondria, as well as therapeutic approaches aimed at stimulating ketogenesis are investigated. The role of insulin resistance in the brain in the development of BA is studied.

8. The role of intestinal microbioma. More and more data indicates that the intestinal microbia can affect the function of the brain and the risk of BA. Dysbacteriosis, or violation of the composition of the microbioma, can lead to an increase in the permeability of the intestinal barrier and the penetration of pro -inflammatory molecules into the bloodstream. These molecules can reach the brain and contribute to inflammation and neurodegeneration. Actual studies study the relationship between the composition of the microbioma, inflammation and the risk of BA. For example, probiotics and prebiotics are investigated, which can improve the composition of the microbioma and reduce inflammation. The role of metabolites of microbioma, such as short -chain fatty acids, is studied in the protection of the brain.

II. Diagnostics and biomarkers:

1. Neurousualization: Pat and MRI. Positron emission tomography (PET) and magnetic resonance tomography (MRI) play an important role in the diagnosis of BA. PET allows you to visualize Aβ plaques and NFK in the brain using special radio leagues. MRI allows you to evaluate the structure of the brain, identify atrophy and vascular lesions. Actual studies are aimed at developing new radio -heading for PET, which are more specific to various forms of Aβ and Tau. New MRI methods are also developed, which allow you to identify the early signs of neurodegeneration, such as changes in the microstructure of white matter. Multimodal neuroimaging, combining PET and MRI, can provide a more complete picture of the pathology of BA.

2. Biomarkers of cerebrospinal fluid (SMZH). Analysis of CMS allows you to measure the levels of Aβ42, Tau and phosphorized Tau. A decrease in the level of Aβ42 and an increase in the levels of TAU and phosphorized Tau are signs of BA. SMZH biomarkers can be useful for early diagnostics of BA, especially in people with mild cognitive disorders. Actual research is aimed at developing new SMZh biomarkers, which are more sensitive and specific to BA. Also, the possibility of using biomarkers of the SMS is also studied to predict the progression of the disease.

3. Blood biomarkers: new prospects. The development of blood biomarkers for BA is an important task, as this will allow screening of the population and identify people with an increased risk of disease in the early stages. Recent studies have identified several blood proteins, which can be associated with BA, including Aβ, Tau and neurofilaments. Actual research is aimed at the validation of these biomarkers in large cohorts of patients and at the development of highly sensitive and specific blood tests for BA. A promising area is the use of technologies, such as a supersensitive immunosorbent test (SIMOA), to measure low concentrations of proteins associated with BA, in the blood.

4. Cognitive testing and neuropsychological assessment. Cognitive testing and neuropsychological assessment are an important part of the diagnosis of BA. These tests allow you to evaluate various cognitive functions, such as memory, attention, speech and executive functions. Actual research is aimed at developing new cognitive tests that are more sensitive to the early signs of BA. The possibility of using cognitive tests for monitoring the progression of the disease and evaluating the effectiveness of treatment is also studied. Computer cognitive tests are developed, which can be used to remove cognitive functions.

5. Differential diagnosis: differences from other dementia. It is important to distinguish the BA from other forms of dementia, such as vascular dementia, front-and-bee dementia and dementia with Levy Taurus. Differential diagnosis is based on a combination of clinical data, neuroizoalization and biomarkers. Actual research is aimed at developing more accurate criteria for differential diagnosis of various forms of dementia. The role of genetic factors in the development of various forms of dementia is studied.

6. Artificial intelligence (AI) and machine learning in diagnosis. AI and machine learning can be used to analyze large volumes of data, such as neuroizualization, biomarkers and cognitive tests, to improve BA diagnosis. AI can help identify the early signs of the disease, predict the progression of the disease and differentiate BA from other forms of dementia. Actual research is aimed at developing and validating machine learning algorithms for BA.

7. Diagnostics at the preclinical stage. The development of methods for diagnosing BA at the preclinical stage when there is no clinical symptoms yet is an important task for the early start of treatment and preventing the progression of the disease. For diagnosis at the preclinical stage, neuroimaging and biomarkers of the SMZH are used. Actual studies are aimed at identifying risk factors for BA and the development of strategies for the prevention of disease in people with increased risk.

III. Therapeutic strategies and clinical trials:

1. Cholinesterase and memantine inhibitors: symptomatic treatment. Cholinesterase inhibitors (prenepsil, rivastigmin, galantamine) and memantine are drugs that are used for symptomatic treatment of BA. Holinerase inhibitors increase the level of acetylcholine in the brain, which improves cognitive functions. Memantin blocks NMDA receptors, which protects neurons from exaytotoxicity. Actual studies are aimed at developing new drugs for symptomatic treatment of BA, which have higher effectiveness and less side effects.

2. Anti -amyloid therapy: the latest achievements and failures. Anti -amyloid therapy is aimed at reducing the level of Aβ in the brain. Several anti -amyloid drugs passed clinical trials, but most of them did not show significant effectiveness in slowing the progression of BA. Recently, two antibodies, adukanumab and healer, received the approval of FDA for the treatment of BA. Adukanumab showed the ability to reduce the level of Aβ in the brain, but its clinical effectiveness remains controversial. Lekanemab also reduces the level of Aβ and showed a slight slowdown in cognitive deterioration in clinical trials. Actual studies are aimed at developing more effective anti -amyloid drugs, as well as to identify patients who may get the greatest benefit from this treatment. The effect of anti-amyloid therapy on Tau-pathology and inflammation is studied.

3. Antitau-therapy: new approaches. Antitau-therapy is aimed at preventing the formation of NFK or the removal of existing NFCs. Several antitau-preparations are in development, including Tau aggregation inhibitors, microtubules and antibodies to Tau. Actual research is aimed at assessing the safety and efficiency of antitau-preparations in clinical trials. The effect of antitau-therapy on cognitive functions and neurodegeneration is studied.

4. Anti -inflammatory drugs and immunomodulation. Anti -inflammatory drugs and immunomodulation can help reduce inflammation in the brain and slow down the progression of BA. Several anti -inflammatory drugs passed clinical trials, but the results were ambiguous. Actual studies are aimed at identifying patients who may be most beneficial from anti -inflammatory therapy, as well as the development of more effective anti -inflammatory drugs. The role of microlytes and astrocytes in inflammation with BA is studied.

5. Stem cell therapy and gene therapy. Stem cell therapy and gene therapy are promising areas for the treatment of BA. Stem cell therapy can help restore damaged neurons and improve brain function. Gene therapy can be used to deliver genes that encode neurotrophic factors or enzymes that break down Aβ and Tau. Actual research is aimed at developing safe and effective methods of stem cells and gene therapy for BA.

6. Medicines that improve brain metabolism and energy metabolism. Preparations that improve brain metabolism and energy metabolism can help compensate for a decrease in glucose metabolism in the brain. Several drugs, such as Coenzym Q10 and Creatine, are in development for the treatment of BA. Actual research is aimed at assessing the effectiveness of these drugs in clinical trials. The role of a ketogenic diet is studied in improving the metabolism of the brain with BA.

7. Life and prevention: diet, physical exercises, cognitive stimulation. Changes in lifestyle, such as diet, physical exercises and cognitive stimulation, can help reduce the risk of BA and slow down the progression of the disease. The Mediterranean diet, rich in fruits, vegetables, fish and olive oil, is associated with a reduced risk of BA. Physical exercises improve the blood supply to the brain and stimulate neurogenesis. Cognitive stimulation, such as reading, solving crosswords and studying new skills, can help maintain cognitive functions. Actual research is aimed at developing BA prevention programs, which include changes in lifestyle.

8. Search for new targets for drugs. Despite significant progress in the understanding of the pathogenesis of BA, there is still no effective treatment. Therefore, the search for new targets for drugs continues. Various molecular mechanisms are studied that are involved in the development of BA, such as inflammation, oxidative stress, synaptic dysfunction and impaired transport of substances in neurons. New technologies are being developed for the search and development of drugs, such as high -performance screening and computer modeling.

9. Clinical trials: problems and prospects. Conducting clinical trials for the treatment of BA is a difficult task. One of the main problems is the heterogeneity of the disease. BA can be called various factors and manifest itself differently in different people. Therefore, it is important to conduct clinical trials that take into account this heterogeneity and allow you to identify patients who can get the most benefit from specific treatment. Another problem is that many clinical trials begin in the later stages of the disease, when brain damage is already irreversible. Therefore, it is important to begin treatment in the early stages of the disease, when it is still possible to prevent or slow down the progression of neurodegeneration.

IV. Alzheimer’s patient care and family support:

1. Multidisciplinary Care approach. Care for patients BA requires a multidisciplinary approach, including doctors, nurses, social workers, psychologists and other specialists. A multidisciplinary team can help patients and their families cope with physical, cognitive and emotional problems associated with BA. It is important to provide patients with access to quality medical care, rehabilitation and social support.

2. Management of cognitive and behavioral symptoms. BA causes not only cognitive disorders, but also behavioral symptoms, such as depression, anxiety, apathy, irritability, aggression and wandering. Management of these symptoms is an important part of the care of patients with BA. There are medicinal and non -drug methods for managing behavioral symptoms. It is important to create a safe and comfortable atmosphere for patients, as well as provide them with regular physical activity and cognitive stimulation.

3. Support for guardians and families. Care for patients with BA is a heavy burden for guardians and families. Guardians often experience physical, emotional and financial exhaustion. It is important to provide guardians and families with access to information, education and support. There are support groups for guardians where they can communicate with other people who are faced with similar problems. It is also important that the guardians have the opportunity to relax and take care of themselves.

4. Technologies for improving care and monitoring. Technologies can help improve BA patients and make life easier for guardians. There are various applications and devices that can help patients navigate space, remind you of taking medication and maintaining communication with loved ones. Monitoring systems are also developed that can monitor the condition of the patients and prevent guardians about the occurrence of problems.

5. Ethical issues and decision making. Care for patients BA raises a number of ethical issues, such as making decisions on medical care, care and disposal of property. It is important that patients have the opportunity to express their wishes for care and treatment in the early stages of the disease, when they are still able to make decisions. It is also important that guardians and families observe the rights and dignity of patients.

V. The future studies of Alzheimer’s disease:

1. Personalized medicine. The future of BAS research is associated with the development of personalized medicine. This means that treatment will be developed taking into account the individual characteristics of each patient, such as genetics, lifestyle and stage of the disease. Personalized medicine can help increase the effectiveness of treatment and reduce the risk of side effects.

2. Prevention and early intervention. Prevention and early intervention are key strategies to combat BA. The study of risk factors for BA and the development of prevention strategies can help reduce incidence and delay the progression of the disease. Early detection of BA and the onset of treatment in the early stages of the disease can help preserve cognitive functions and improve the quality of life of patients.

3. New technologies and innovative approaches. The development of new technologies and innovative approaches, such as AI, machine learning, genetic therapy and stem cells, can open new opportunities for the treatment of BA. It is important to maintain research in these areas and develop new methods of diagnosis and treatment of BA.

4. International cooperation and data exchange. The solution to the problem of BA requires international cooperation and data exchange between scientists and researchers from around the world. Data exchange can help accelerate research and develop more effective methods for diagnosis and treatment of BA. It is important to create international platforms for data exchange and cooperation in the field of BA research.

5. Increased awareness and education. Increasing the awareness of BA and the formation of the population is an important task. It is necessary to inform people about risk factors, the early signs of the disease and the possibilities of prevention and treatment. It is also important to train medical workers and guardians skills in caring for patients with BA.