Capillary dysfunction correlates with cortical amyloid load in early Alzheimer's disease

Area of Science:

• Neuroscience
• Radiology
• Biomedical Engineering

Background:

• Cerebral perfusion alterations are implicated in Alzheimer's disease (AD) pathogenesis.
• Amyloid-beta (Aβ) accumulation and microvascular dysfunction may lead to cerebral hypoxia in AD.

Purpose of the Study:

• To investigate cerebral circulation changes in prodromal AD (pAD).
• To examine the relationship between Aβ load and cerebral perfusion in pAD.

Main Methods:

• Dynamic susceptibility contrast MRI and Positron Emission Tomography (PET) were used.
• Cerebral perfusion and Aβ levels were assessed in individuals with mild cognitive impairment (MCI) and high Aβ load (pAD-MCI), MCI without AD pathology, and healthy controls.

Main Results:

• The pAD-MCI group exhibited significantly reduced microvascular blood flow and increased heterogeneity of microvascular blood transit times compared to controls.
• In pAD-MCI, elevated Aβ levels were associated with decreased microvascular blood flow and increased heterogeneity in frontal and temporal regions.

Conclusions:

• A strong link exists between Aβ deposition levels and brain microvascular perfusion in pAD.
• A potential vicious cycle is suggested where Aβ load and impaired brain perfusion reinforce each other, contributing to AD progression.