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The main pathological features of AD are \u03b2\u2010amyloid protein (A\u03b2) deposition and tau protein hyperphosphorylation. Currently, there are no effective drugs for the etiological treatment of AD. Rifampicin (RIF) is a semi\u2010synthetic broad\u2010spectrum antibiotic with anti\u2010\u03b2\u2010amyloid deposition, anti\u2010inflammatory, anti\u2010apoptosis, and neuroprotective effects, but its application in AD treatment has been limited for its strong hydrophobicity, high toxicity, short half\u2010life, low bioavailability, and blood\u2013brain barrier hindrance. We designed a novel brain\u2010targeted and MRI\u2010characteristic nanomedicine via loading rabies virus protein 29 (RVG29), rifampicin, and Gd on poly (\n                    <jats:sc>l<\/jats:sc>\n                    \u2010lactide) nanoparticles (RIF@PLA\u2010PEG\u2010Gd\/Mal\u2010RVG29). The cytotoxicity assay demonstrated that RIF@PLA\u2010PEG\u2010Gd\/Mal\u2010RVG29 had favorable biocompatibility and security. Fluorescence imaging in vivo showed that PLA\u2010PEG\u2010Gd\/Mal\u2010RVG29 could deliver rifampicin into the brain by enhancing cellular uptake and brain targeting performance, leading to improvement of the bioavailability of rifampicin. In in vivo study, RIF@PLA\u2010PEG\u2010Gd\/Mal\u2010RVG29 improved the spatial learning and memory capability of APP\/PS1 mice in the Morris water maze, as compared to rifampicin. Immunofluorescence, TEM, immunoblotting, and H&amp;E staining revealed that RIF@PLA\u2010PEG\u2010Gd\/Mal\u2010RVG29 reduced A\u03b2 deposition in hippocampal and cortex of APP\/PS1 mice, improved the damage of synaptic ultrastructure, increased the expression level of PSD95 and SYP, as well as reduced the necrosis of neurons. These findings suggest that RIF@PLA\u2010PEG\u2010Gd\/Mal\u2010RVG29 may be an effective strategy for the treatment of AD.\n                  <\/jats:p>","DOI":"10.1002\/btm2.10395","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T04:29:11Z","timestamp":1661228951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Targeted brain delivery of\n                    <scp>RVG29\u2010modified rifampicin\u2010loaded<\/scp>\n                    nanoparticles for Alzheimer's disease treatment and diagnosis"],"prefix":"10.1002","volume":"7","author":[{"given":"Ruiyi","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital, Jinan University  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of 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