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Abstract

Introduction

Alzheimer’s disease is characterized by a complex and multifactorial pathogenesis, involving key features such as amyloid-beta plaques, tau tangles, and neuron loss. Understanding the disease requires investigating its underlying causes, as these hallmarks reflect the intricate physiological processes involved. Identifying the root factors driving AD is essential for developing effective treatments.

Method

This literature review was conducted using PubMed and Scopus databases, covering studies published from October 1999 to April 2025. The review included 190 references focused on the pathophysiology of Alzheimer's disease (AD). The selected studies analysed the primary pathophysiology leading to AD, particularly the accumulation of amyloid-beta plaques, tau tangles, and neuronal loss.

Result

The study highlights several key biological factors associated with Alzheimer's Disease (AD). These include genetic mutations, mitochondrial dysfunction, hormonal imbalances, inflammation, oxidative stress, cellular division abnormalities, and reduced levels of dopamine-related neurotransmitters. It also highlights issues with calcium regulation and the imbalance of metals, such as copper, iron, lead, and zinc, in the body. Lifestyle choices such as drinking alcohol and smoking, along with changes in blood vessels and problems with the blood-brain barrier, were also found to play a role in how the disease develops. Additionally, the presence of certain pathogens was suggested as a possible factor in the disease's underlying mechanisms.

Discussion

The results indicate that a complex combination of genetic, biochemical, and environmental factors shapes the development and progression of Alzheimer's disease. Genetic mutations seem to play a significant role in affecting enzyme functions, which can disrupt vital biological processes. Problems with mitochondria and hormonal imbalances contribute to the deterioration of nerve cells, while oxidative stress and neuroinflammation are key mechanisms that worsen cellular damage. Disruptions in calcium signalling and imbalances in bio-metals further disturb neuronal stability. Lifestyle choices, blood vessel issues, and blood-brain barrier problems highlight the multifaceted nature of the disease. The study also highlights the close relationship between oxidative stress and neuroinflammation, suggesting that they may form a feedback loop that accelerates disease progression. Additionally, the possible involvement of infectious agents adds another layer of complexity, indicating that infections might trigger or worsen neurodegeneration in vulnerable individuals.

Conclusion

To better understand and address Alzheimer’s disease, it is essential to examine the fundamental processes that trigger its development. The various and interconnected factors involved—such as genetic mutations, cellular problems, environmental factors, and exposure to pathogens—require a comprehensive and integrated approach to research and treatment. Recognizing that neuroinflammation and oxidative stress play key roles in the progression of the disease can help guide future efforts toward early detection and more precise interventions.

© 2025 Bentham Science Publishers
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A Review on the Pathophysiology of Alzheimer’s Disease
Bentham Science Publishers ; https://doi.org/10.2174/0113892037416859250915091846
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  • Article Type:     Review Article
Keywords: neurofibrillary tangles ; Alzheimer’s disease ; neuron loss ; beta-amyloid peptide ; pathophysiology ; neuroinflammation

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