Major Research Findings

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder that causes cognitive decline in old age. In its early stages, AD is associated with microstructural abnormalities in white matter (WM). study used multiple indices of diffusion tensor imaging (DTI) and brain volumetric measurements to comprehensively investigate the landscape of AD pathology. The sample comprised 58 individuals including cognitively normal subjects (controls), amnestic mild cognitive impairment (MCI) and AD patients. Relative to controls, both MCI and AD subjects showed widespread changes of anisotropic fraction (FA) in the corpus callosum, cingulate and uncinate fasciculus. Mean diffusivity and radial changes were also observed in AD patients in comparison with controls. After controlling for the gray matter atrophy the number of regions of significantly lower FA in AD patients relative to controls was decreased; nonetheless, unique areas of microstructural damage remained, e.g. the corpus callosum and uncinate fasciculus.

study showed that endoplasmic reticulum (ER) stress plays a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD). This study examined whether the expression of Syx5 is altered by ER stress. De novo synthesis of ER-Golgi SNARE Syx5 and Bet1 was induced by various ER stressors. Elevated expression of Syx5 and Bet1 was associated with increased levels of these proteins in vesicular components, including ER-Golgi-intermediate-compartment/vesicular tubular clusters. In addition, ER stress diminished amyloid β (Aβ) peptide secretion. Knockdown of Syx5 expression enhanced the secretion of Aβ peptides under condition without ER stress. Moreover, diminished Aβ peptide secretion resulting from ER stress was significantly reversed by Syx5 knockdown. These findings suggest that Syx5 plays important roles in β-amyloid precursor protein processing and in the ER stress response that precedes apoptotic cell death and may be involved in the crosstalk between these two pathways.

Reasons for Causes

There are many causes of Alzheimer's disease, but the specific reasons have been revealed in different aspects by several papers.

General Causes

White Matter Microstructural Abnormalities

study showed that in the early stages of Alzheimer's disease, there are microstructural abnormalities in the white matter. This suggests that damage to the white matter, which is responsible for information transmission between brain nerve cells, could lead to cognitive decline.

ER Stress

study showed that ER stress plays a role in the pathogenesis of Alzheimer's disease. ER stress occurs when protein folding abnormalities occur, and it can lead to cell dysfunction and death.

Accumulation of Amyloid β Peptide

Amyloid β peptide is thought to be one of the causative agents of Alzheimer's disease. study showed that ER stress reduced the secretion of amyloid β peptide. On the other hand, study suggested that presenilin dysfunction is associated with the accumulation of amyloid β peptide. These studies indicate that the accumulation of amyloid β peptide may play an important role in the development of Alzheimer's disease.

Neuroinflammation

Neuroinflammation is considered to be one of the important factors involved in the development and progression of Alzheimer's disease. study pointed out the association between periodontal disease and Alzheimer's disease. Periodontal disease is an infectious disease accompanied by gum inflammation, but it is believed that the inflammation can cause neuroinflammation, leading to the development of Alzheimer's disease.

Aging

study pointed out that the risk of Alzheimer's disease increases with aging. study suggests that various cellular functions decline with aging, which could increase the risk of developing Alzheimer's disease.

Gene Mutation

Some Alzheimer's disease is thought to be caused by gene mutations. study showed that mutations in the presenilin gene are associated with the development of Alzheimer's disease. Gene mutation is one of the factors that increase the risk of developing Alzheimer's disease.

Oxidative Stress

Oxidative stress is a major factor that can lead to cell dysfunction and death. study suggested that plasmalogens may play an important role in protecting cells from oxidative stress. Oxidative stress is one of the factors involved in the development and progression of Alzheimer's disease.

Countermeasures for Causes

Lifestyle Improvement

Improving lifestyle, such as diet therapy and exercise therapy, is important to reduce the risk of developing Alzheimer's disease. study showed that bajijiasu has neuroprotective effects in a rat model of Aβ₂₅₋₃₅-induced neurotoxicity. Bajijiasu is an ingredient used in traditional Chinese medicine. Improving lifestyle, such as diet therapy and exercise therapy, can not only reduce the risk of developing Alzheimer's disease, but also has the potential to have neuroprotective effects.

Neuroprotective Drugs

Neuroprotective drugs are drugs that prevent nerve cell death and suppress cognitive decline. study suggested that APC/Cdh E3 ubiquitin ligase plays a role in the pathophysiology of Alzheimer's disease. APC/Cdh E3 ubiquitin ligase is an enzyme involved in intracellular protein degradation. This study suggests the potential for the development of neuroprotective drugs that target APC/Cdh E3 ubiquitin ligase.

Antioxidants

Antioxidants have the effect of protecting cells from oxidative stress. 2 study suggested that antioxidants could help maintain memory in seniors. Antioxidants not only reduce the risk of developing Alzheimer's disease but also have the potential to suppress cognitive decline.

Comparison Between Studies

Commonalities of Studies

Multiple studies have shown that white matter microstructural abnormalities, ER stress, accumulation of amyloid β peptide, neuroinflammation, and aging are involved in the pathophysiology of Alzheimer's disease. These studies show that the pathophysiology of Alzheimer's disease is very complex and that multiple factors are involved in a complex manner.

Differences of Studies

Each study has been conducted from a different perspective on the factors involved in the development and progression of Alzheimer's disease and their mechanisms. For example, study focused on white matter microstructural abnormalities, while study focused on ER stress. As each study focuses on different points, it is necessary to consider the results of multiple studies comprehensively to gain a deeper understanding of the pathophysiology of Alzheimer's disease.

Cautions for Applying the Research to Real Life

The causes and mechanisms of Alzheimer's disease have not yet been fully elucidated. Therefore, there is currently no way to completely cure Alzheimer's disease. However, methods have been developed to reduce the risk of developing the disease or to slow its progression, such as lifestyle improvements and drug therapy. By practicing these methods appropriately, it is expected to reduce the risk of developing Alzheimer's disease or to suppress cognitive decline.

Limitations of Current Research

Current research has not yet fully elucidated the causes and mechanisms of Alzheimer's disease. Also, effective treatments are limited. Future research is expected to develop methods for preventing and treating Alzheimer's disease.

Directions for Future Research

The following research is needed to develop prevention and treatment methods for Alzheimer's disease.

• Elucidation of the mechanisms of Alzheimer's disease development
• Development of new treatment drugs
• Development of new treatment methods such as gene therapy and cell therapy

Conclusion

Alzheimer's disease is a serious disease that causes cognitive decline in the elderly. The cause of onset is multifaceted and not yet fully understood. However, various research has been progressing in recent years, and methods have been developed to reduce the risk of onset or to slow its progression. By practicing these methods appropriately, it is expected to reduce the risk of developing Alzheimer's disease or to suppress cognitive decline.

Alzheimer's disease is a disease that has a major impact on not only the patients themselves but also their families and society. It is important to deepen our understanding of Alzheimer's disease and to promote the development of preventive and therapeutic methods.