Capsid engineering enables AAV retargeting, and a CNS-tropic variant such as AAV.PHP.eB enables robust transduction of the brain and spinal cord. Yet AAV.PHP.eB derives from AAV9, and high-dose systemic AAV9 has been linked to serious, dose-dependent adverse events, highlighting the need to limit off-target exposure. Prednisolone is often used to blunt anti-AAV immunity, but prior work shows that it can increase liver transduction, undermining CNS selectivity. We therefore sought an adjuvant that preserves or enhances CNS delivery while reducing hepatic uptake. We identify AGT-01 as such a candidate. In mice, AGT-01 increased AAV.PHP.eB-mediated reporter expression in the CNS and lowered liver transduction relative to vehicle and prednisolone. With a therapeutic payload (AAV.PHP.eB–Donanemab), AGT-01 improved brain distribution and tissue protein levels while limiting hepatic exposure. Mechanistically, both AGT-01 and prednisolone increased Ly6a transcripts in primary neural cultures, consistent with a cell-intrinsic component of Ly6a-mediated entry. AGT-01 also inhibited autophagy, and under fasting or glucose deprivation it produced additional gains in CNS transduction. These data support AGT-01 as a CNS-directed adjuvant for AAV.PHP.eB that maintains tropism, boosts expression, and reduces hepatic off-targeting, offering a potential alternative to prednisolone.