Semimechanistic Population Pharmacokinetic Modeling to Investigate Amyloid Beta Trafficking and Accumulation at the BBB Endothelium.

ABSTRACT: Elevated exposure to toxic amyloid beta (Aβ) peptides and consequent blood-brain barrier (BBB) dysfunction are believed to promote vasculopathy in Alzheimer's disease (AD). However, the accumulation kinetics of different Aβ isoforms within the BBB endothelium and how it drives BBB dysfunction are not clearly characterized. Using single positron emission computed tomography (SPECT)-computed tomography (CT) dynamic imaging coupled with population pharmacokinetic modeling, we investigated the accumulation kinetics of Aβ40 and Aβ42 in the BBB endothelium. Brain clearance was quantified after intracerebral administration of ¹²⁵I-Aβ, and BBB-mediated transport was shown to account for 54% of ¹²⁵I-Aβ40 total clearance. A brain influx study demonstrated lower values of both m

SUBMITTER: Wang Z 

PROVIDER: S-EPMC9113734 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature