Novel method for down-regulation of amyloid

A method for in vivo down-regulation of amyloid precursor protein (APP) or beta amyloid (Aβ) in an animal, including a human being, the method comprising effecting presentation to the animal's immune system of an immunogenically effective amount of at least one analogue of APP or Aβ that incorporates into the same molecule at least one B-cell epitope of APP and/or Aβ and at least one foreign T-helper epitope (TH epitope) so that immunization of the animal with the analogue induces production of antibodies against the animal's autologous APP or Aβ, wherein the analogue

• a) is a polyamino acid that consists of at least one copy of a subsequence of residues 672-714 in SEQ ID NO:
• 2, wherein the foreign TH epitope is incorporated by means of amino acid addition and/or insertion and/or deletion and/or substitution, wherein the subsequence is selected from the group consisting of residues 1-42, residues 1-40, residues 1-39, residues 1-35, residues 1-34, residues 1-28, residues 1-12, residues 1-5, residues 13-28, residues 13-35, residues 17-28, residues 25-35, residues 35-40, residues 36-42 and residues 35-42 of the amino acid sequence consisting of amino acid residues 673-714 of SEQ ID NO:
• 2;
• and/or
• b) is a polyamino acid that contains the foreign TH epitopes and a disrupted APP or Aβ sequence so that the analogue does not include any subsequence of SEQ ID NO:
• 2 that binds productively to MHC class II molecules initiating a T-cell response;
• and/or
• c) is a polyamino acid that comprises the foreign TH epitope and APP or Aβ derived amino acids, and comprises 1 single methionine residue located in the C-terminus of the analogue, wherein other methionine residues in APP or Aβ and in the foreign TH epitope have been substituted or deleted, and preferably have been substituted by leucin or isoleucine;
• and/or
• d) is a conjugate comprising a polyhydroxypolymer backbone to which is separately coupled a polyamino acid as defined in a) and/or a polyamino acid as defined in b) and/or a polyamino acid as defined in c);
• and/or
• e) is a conjugate comprising a polyhydroxypolymer backbone to which is separately coupled 1) the foreign TH epitope and 2) a polyamino acid selected from the group consisting of a subsequence as defined in a), a disrupted sequence of APP or Aβ as defined in b), and an APP or Aβ derived amino acid sequence that comprises 1 single methionine residue located in the C-terminus, wherein other methionine residues in APP or Aβ and in the foreign TH epitope have been substituted or deleted, and preferably have been substituted by leucin or isoleucine.