Capillary dysfunction in healthy elderly APOE ε4 carriers with raised brain Aβ deposition

Area of Science:

• Neuroscience
• Cardiovascular Research
• Medical Imaging

Background:

• Alzheimer's disease (AD) is linked to microvascular circulation disturbances.
• Capillary dysfunction may be an underappreciated contributor to AD pathogenesis.
• Investigating microvascular changes offers potential insights into AD development.

Purpose of the Study:

• To investigate microvascular blood flow and capillary dysfunction in preclinical and prodromal AD.
• To assess the presence and progression of capillary dysfunction across the AD continuum.
• To explore the relationship between capillary dysfunction, beta-amyloid (Aβ) deposition, and AD development.

Main Methods:

• Utilized dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and positron emission tomography (PET).
• Examined microvascular circulation alterations in two independent cohorts of APOE ε4 carriers.
• Compared capillary dysfunction levels between preclinical AD, prodromal AD, and age-matched controls.

Main Results:

• Capillary dysfunction was significantly elevated in both preclinical and prodromal AD individuals compared to controls.
• Prodromal AD individuals showed higher levels of capillary dysfunction than preclinical AD individuals.
• Capillary dysfunction is detectable at the preclinical stage and worsens throughout the AD continuum.

Conclusions:

• Capillary dysfunction is an early and progressive feature of Alzheimer's disease.
• Understanding capillary dysfunction's role may illuminate the link between cardiovascular risk and AD.
• Targeting capillary dysfunction could offer novel therapeutic strategies for AD.