Amyloid beta(1-42) oligomers, derivatives thereof and antibodies thereto, methods of preparation thereof and use thereof

An isolated antibody which binds an N-terminal truncated amyloid-β (“Aβ”)(1-42) oligomer comprising an Aβ(X-42) fragment, wherein X is 10 to 24, the isolated antibody obtainable by a method comprising:

• a) immunizing a host with the N-terminal truncated Aβ(1-42) oligomer;
• and
• b) obtaining an antibody-containing host serum produced as a response to said immunization,
• wherein the isolated antibody binds the N-terminal truncated Aβ(1-42) oligomer with 10-fold greater affinity than an amyloid derived, diffusible and dementing ligand (ADDL),
• wherein the N-terminal truncated Aβ(1-42) oligomer is produced by a process comprising:
• i) exposing a monomeric Aβ(1-42) protein to a detergent to form an intermediate oligomer;
• ii) reducing the detergent action and further incubating the intermediate oligomer to form an Aβ(1-42) oligomer;
• and
• iii) treating the Aβ(1-42) oligomer with a protease to form the N-terminal truncated Aβ(1-42) oligomer,
• wherein the detergent is a compound of formula R—X, wherein the radical R is unbranched or branched alkyl having from 6 to 20 carbon atoms or unbranched or branched alkenyl having from 6 to 20 carbon atoms, and the radical X is an acidic group or salt thereof.