Cooperation between neurovascular dysfunction and Aβ in Alzheimer's disease

Area of Science:

• Neuroscience
• Neurology
• Vascular Biology

Background:

• The amyloid-β (Aβ) hypothesis, once central to Alzheimer's disease (AD) pathogenesis, is increasingly challenged by clinical trial failures.
• Emerging evidence indicates vascular system dysfunction plays a critical role in AD, with vascular damage potentially preceding Aβ and neurofibrillary tangle (NFT) deposition.

Purpose of the Study:

• To review the intricate relationship between amyloid-β (Aβ) and neurovascular function in Alzheimer's disease (AD).
• To explore the role of vascular dysfunctions as a potential trigger or contributor to AD.
• To highlight the importance of the neurovascular unit (NVU) in understanding AD pathophysiology.

Main Methods:

• Review of recent scientific literature on Alzheimer's disease (AD) and vascular contributions.
• Analysis of studies investigating changes in vascular hemodynamics, cell function, coverage, and blood-brain barrier (BBB) permeability in AD.
• Examination of the interaction between Aβ and the neurovascular unit (NVU).

Main Results:

• Alzheimer's disease (AD) is associated with diverse vascular dysfunctions, including altered hemodynamics, cellular function, vascular coverage, and blood-brain barrier (BBB) permeability.
• Vascular defects can precipitate Aβ deposition, neurotoxicity, glial activation, and metabolic dysfunction.
• Aβ and oxidative stress exacerbate vascular damage, creating a detrimental feedback loop.

Conclusions:

• The neurovascular unit (NVU) interaction is crucial for understanding Alzheimer's disease (AD) pathophysiology.
• Vascular dysfunction is a significant factor in AD, potentially preceding or interacting with Aβ pathology.
• Targeting vascular health may offer new therapeutic strategies for Alzheimer's disease (AD).