I. Introduction
The blood-brain barrier (BBB) is a physical barrier that keeps the extracellular fluid of the brain separate from the bloodstream. Its primary job is to carefully control the flow of chemicals from the blood to the brain and to prevent entry of pathogens and immune cells, preserving a steady environment for healthy neuronal activity. The BBB deteriorates in AD for a number of reasons, which may include the buildup of amyloid-beta and tau protein pathology. These aberrant protein aggregates can cause oxidative stress and inflammation, both of which can compromise the BBB's integrity. Increased permeability brought on by this defective barrier may allow the passage of dangerous chemicals, pathogens and immune cells into the brain. As a result, neuroinflammation and neuronal damage may worsen, advancing the pathology of AD and cognitive loss. The connection between the BBB and AD emphasizes how crucial it is to comprehend the malfunction of the barrier and maybe target it in order to create novel therapeutic methods for treating the condition.
II. AD - The Top Neurodegenerative Disorder
Symptom’s
AD is a progressive and irreversible neurological disorder that affects the brain, primarily causing problems with memory, thinking, and behavior. It is the most common cause of over 55 million cases of dementia in older adults worldwide, with 10 million new dementia patients per year. (WHO, 2023) While the exact cause of Alzheimer's is not fully understood, it is believed to be a complex interplay of genetic, environmental, and lifestyle factors.
Early symptoms may include mild forgetfulness and difficulty recalling recent events or names. As the disease advances, individuals may experience confusion, disorientation, and difficulty with problem-solving and language. They may struggle to complete familiar tasks, misplace items, and experience changes in mood or personality. As Alzheimer's progresses, individuals may have difficulty recognizing family and friends, exhibit significant memory loss, and require assistance with daily activities. Ultimately, the disease leads to severe cognitive impairment, loss of independence, and challenges with basic bodily functions, making it one of the most common causes of dementia in older adults. (Mayo Clinic, 2023)
Possible Causes And Disease Targets
AD is a complex and multifactorial neurodegenerative disorder, and its exact cause remains unclear. Several hypotheses have been proposed by researchers to explain the origins and contributing factors of AD. Here is a summary of some major alternative hypotheses:
Amyloid Hypothesis: The amyloid hypothesis is one of the most well-known theories regarding AD. It suggests that the accumulation of amyloid-beta protein in the brain, leading to the formation of amyloid plaques, is a central cause of the disease. According to this hypothesis, the aggregation of amyloid-beta disrupts brain cell function and leads to neurotoxicity, ultimately contributing to cognitive decline. (Zhang, 2023)
Tau Hypothesis: Another prominent theory focuses on the role of tau protein. In AD, tau protein forms abnormal tangles inside neurons, disrupting the cell's structure and function. The tau hypothesis suggests that these tangles play a crucial role in neurodegeneration and cognitive decline. (Zhou, 2013)
Cholinergic Hypothesis: This hypothesis posits that AD is associated with a significant decrease in cholinergic neurotransmission. The cholinergic system is responsible for producing and releasing the neurotransmitter acetylcholine, which is crucial for memory and cognitive functions. The cholinergic hypothesis suggests that the degeneration of cholinergic neurons contributes to memory deficits in Alzheimer's patients. (Vrabec, 2023)
Oxidative Stress and Inflammation: Some researchers propose that oxidative stress and chronic inflammation in the brain may contribute to AD. Oxidative stress refers to an imbalance between the ...
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