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bioRxiv · 10.64898/2026.03.19.712819

Expression of amyloid-β antibody via AAV of CNS tropism alleviates Alzheimer's disease in mice

Dai, Z.-M.·Min Jiang, M.·Yin, W.·Wang, Z.·Zhu, X.-J.·Qiu, M.
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Abstract

Alzheimers disease (AD), the leading cause of dementia, affects over 33 million people worldwide, with pathogenesis tied to amyloid-{beta} (A{beta}) accumulation. Although anti-A{beta} monoclonal antibodies have shown clinical benefits, they often cause side effects including amyloid-related imaging abnormalities and brain microhemorrhage, especially in APOE E4 allele carriers. Here we used PHP.eB serotype adeno-associated virus (AAV), a vector with enhanced central nervous system (CNS) tropism, to deliver an A{beta} antibody expression vector (AAV-LEC) into the CNS of APP/PS1 and 5xFAD mice intravenously. The AAV-LEC-mediated expression of anti-A{beta} antibodies in the CNS significantly reduced the number and size of A{beta} plaques at various stages in both APP/PS1 and 5xFAD mice, alongside improved spatial learning and memory. It also reversed abnormal glial activation with reduced disease-associated microglia and astrocytes, and restored oligodendrocyte differentiation and myelin formation. No brain microhemorrhage or liver damage was detected following the AAV-antibody treatment. Thus, this AAV-mediated strategy offers a promising, convenient and safe AD therapeutic approach in the future.

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Dai, Z.-M., Min Jiang, M., Yin, W., Wang, Z., Zhu, X.-J., Qiu, M.. 2026-03-20. Expression of amyloid-β antibody via AAV of CNS tropism alleviates Alzheimer's disease in mice. https://doi.org/10.64898/2026.03.19.712819

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