The invention provides a composition comprising transthyretin and an ICAM-1 targeting agent, wherein the transthyretin and ICAM-1 targeting agent are coupled together, as well as methods of preparing such compositions. The invention further provides a diabody capable of binding specifically to ICAM-1 and transthyretin. The invention also provides a method of use of such composition in the manufacture of a medicament for treating an amyloid-β related neurodegenerative disease, comprising administering to a subject a composition comprising transthyretin coupled to an ICAM-1 targeting agent in an amount effective to treat the neurodegenerative disease, wherein the composition is administered to the subject outside of the blood-brain barrier.