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Dissecting the interface of the blood-brain barrier (BBB) to study Alzheimer's disease

Dynamic and complex interactions between the endothelial cells, neurons, glial cells, and other components are crucial for maintaining the homeostasis of the brain's microenvironment, and its dysfunction is increasingly recognized as a contributing factor to the pathogenesis of AD.

Key Areas of Focus:

  1. Blood-Brain Barrier Dysfunction in Alzheimer's Disease:

    • The BBB is a selective barrier that regulates the passage of molecules between the bloodstream and the brain. In Alzheimer's disease, evidence suggests that BBB integrity is compromised, leading to increased permeability. This allows potentially harmful substances such as blood-derived proteins, inflammatory mediators, and immune cells to enter the brain, which can contribute to neuroinflammation, neuronal damage, and the progression of AD.

  2. Amyloid-β Clearance Mechanisms:

    • The BBB plays a critical role in the clearance of amyloid-β (Aβ) from the brain, a hallmark of Alzheimer's disease. Dysfunctional transport mechanisms at the BBB can lead to the accumulation of Aβ in the brain. Understanding how Aβ is transported across the BBB, and how these processes are altered in AD, can provide insights into therapeutic targets aimed at enhancing Aβ clearance.

  3. Neuroinflammation and the BBB:

    • In Alzheimer's disease, chronic neuroinflammation is a significant factor that contributes to disease progression. The interaction between the BBB and the immune system is crucial, as BBB dysfunction can lead to an influx of peripheral immune cells into the brain, exacerbating neuroinflammatory processes. Studying the molecular and cellular changes at the BBB during neuroinflammation can help identify potential therapeutic targets to modulate immune responses in AD.

  4. Vascular Contributions to Alzheimer's Disease:

    • Vascular dysfunction, including reduced cerebral blood flow and microvascular damage, is commonly observed in Alzheimer's disease. The BBB is a key regulator of vascular homeostasis, and its dysfunction can contribute to the vascular pathologies seen in AD. Investigating how vascular changes influence BBB integrity and function in the context of Alzheimer's disease is essential for understanding the vascular contributions to AD pathology.

Anatomical illustration of the human blood-brain barrier interface.png

Anatomical illustration of the blood-brain barrier interface

Study the BBB in Alzheimer's Disease

Studying the BBB in AD.webp

Strategies:

Advanced in vitro and in vivo models, including, brain organoids, brain microphysiological systems (brain-on-a-chip) and transgenic animal models, are essential tools for studying the BBB in the context of Alzheimer's disease. These models allow for the detailed investigation of BBB function, molecular interactions, and the effects of potential therapeutics in a controlled environment.

Therapeutic Strategies Targeting the BBB:

  • Dissecting the BBB interface provides opportunities to develop therapeutic strategies aimed at restoring BBB integrity, enhancing Aβ clearance, and reducing neuroinflammation. Approaches may include the use of small molecules, antibodies, or gene therapy to target specific pathways involved in BBB dysfunction in Alzheimer's disease.

Interface between nervous and peripheral systems
genetic labeling

Many types of neurons

By dissecting the interface of the blood-brain barrier in the context of Alzheimer's disease, researchers can gain a deeper understanding of the mechanisms underlying BBB dysfunction and its contributions to AD pathogenesis. This knowledge is critical for developing effective therapeutic strategies to protect and restore BBB function, ultimately aiming to slow or halt the progression of Alzheimer's disease.

© 2020 proudly created and kindly shared by Dr. Stephen Eacker. 

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