Pulse pressure is associated with plasma amyloid-β transport dysfunction

Area of Science:

• Neurology
• Cardiovascular Science
• Biochemistry

Background:

• Increased pulse pressure (PP) is a known risk factor for Alzheimer's disease (AD) in older adults.
• Peripheral amyloid-beta (Aβ) clearance is closely related to Aβ deposition in the brain, a hallmark of AD.

Purpose of the Study:

• To investigate the association between pulse pressure and plasma amyloid-beta transport function.
• To explore the relationship between PP and plasma levels of Aβ1-40, Aβ1-42, and key transport proteins like soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor for advanced glycation end products (sRAGE).

Main Methods:

• A cross-sectional study involving 1118 participants.
• Quantification of plasma Aβ levels and Aβ transporter expression (sLRP1, sRAGE).
• Multiple linear regression analyses were used to determine relationships between PP and plasma biomarkers, adjusting for various confounding factors.

Main Results:

• Pulse pressure was a significant determinant of higher plasma amyloid-beta 1-40 levels (β=0.059, P=0.036).
• Elevated PP was associated with lower levels of log-transformed sRAGE (β=-0.002, P=0.029), independent of other health metrics.
• sLRP1 and sRAGE showed positive associations with plasma Aβ1-40, and sRAGE was also positively associated with plasma Aβ1-42.

Conclusions:

• Higher pulse pressure is associated with increased plasma amyloid-beta 1-40 and decreased sRAGE in individuals not on antihypertensive medication.
• These findings suggest that pulse pressure may influence peripheral amyloid-beta clearance pathways, potentially contributing to Alzheimer's disease pathogenesis.