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

INTRODUCTION: Capillary dysfunction, characterized by disturbances in capillary blood flow distribution, might be an overlooked factor in the development of Alzheimer's disease (AD). This study investigated microvascular blood flow in preclinical and prodromal AD individuals. METHODS: Using dynamic susceptibility contrast magnetic resonance imaging and positron emission tomography, we examined alterations in microvascular circulation and levels of Aβ deposition in two independent cohorts of APOE ε4 carriers. RESULTS: Capillary dysfunction was elevated in both prodromal and preclinical AD individuals compared to age-matched controls. Additionally, the prodromal group exhibited higher levels of capillary dysfunction compared to the preclinical group. DISCUSSION: These findings suggest that capillary dysfunction can be detected at the preclinical stage of AD and indicates a worsening of capillary dysfunction throughout the AD continuum. Understanding the interaction between capillary dysfunction and Aβ could provide insights into the relationship between cardiovascular risk factors and the development of AD. Highlights: Alzheimer's disease (AD) is associated with disturbances in microvascular circulation. Capillary dysfunction can be detected in preclinical AD. As cognitive symptoms progress in prodromal AD, capillary dysfunction worsens. Capillary dysfunction may impede the clearance of beta-amyloid (Aβ). Capillary dysfunction might contribute to the development of AD.