Targeting soluble Abeta oligomers in the CSF via intrathecal pseudodelivery

Hypothetical changes in Aβ oligomers during disease progression are transferred to the model of AD biomarker changes, according to Jack et al. A peak in sAβOs occurs in the early symptomatic or presymptomatic stage. Apolipoprotein E (APOE) gene ε4 allele carriers show higher oligomer concentrations, with a peak at a more advanced disease stage, but still in the early stages of the disease. Image from Blomeke.

Simulated dynamics of amyloid clearance using intravenous (IV) and intrathecal pseudodelivery of monoclonal antibodies (mAbs). Intrathecal pseudodelivery achieves rapid reduction of soluble Aβ in cerebrospinal fluid (CSF), leading to amyloid PET negativity by month 132. In contrast, intravenous administration reduces soluble Aβ more gradually, achieving PET negativity by month 150.