Although the potential of using rAAV vectors for the long-term delivery of VHH into the CNS has yet to be fully explored, Marino et al. recently provided significant proof of concept for the feasibility of A-MAD strategies, based on VHH delivery, to stop or slow neurodegenerative disease progression, as shown by the disease modifying effects observed in a murine model of AD, following systemic administration of AAV-PHP.B encoding a highly-specific anti-BACE1 VHH (152). Here, BACE1 is linked to Alzheimer disease.