Methods of decreasing amyloid beta (Aβ) plaque deposition and hyperphosphorylated tau plaque deposition in Alzheimer's disease using a cystatin C fusion protein
The present application discloses a method for treating a protein deficiency in the central nervous system of a subject in need thereof, comprising systemically administering to the subject a therapeutically effective dose of a fusion polypeptide comprising the first protein, wherein the fusion polypeptide comprises: (a) the first protein; (b) a second protein that provides extended circulation-lifetime in vivo and (c) blood brain barrier crossing facilitating peptide; wherein the fusion polypeptide crosses the blood brain barrier (BBB).
1. A method for decreasing both amyloid beta (Abeta) plaque deposition and hyperphosphorylated Tau plaque deposition in a brain in a subject suffering from Alzheimer's disease (AD) compared to the Abeta plaque deposition and hyperphosphorylated Tau plaque deposition in the brain of the subject suffering from AD with no treatment, comprising administering systemically to the subject suffering from AD, an effective amount of a recombinantly produced Cystatin C (CysC) fusion polypeptide comprising in N-terminus to C-terminus order, a full length wild type Cystatin C (CysC), a first linker, a Human Serum Albumin protein, a second linker, and a specific cell penetrating peptide, wherein the first linker is GGSAS (SEQ ID NO: 1) or GGGSGGGS (SEQ ID NO:2), the second linker is GFLG (SEQ ID NO:3), and the cell penetrating peptide consists of amino acid residues 715-737 of the amino acid sequence of SEQ ID NO:6; and wherein the effective amount is about 5 mg/kg or 10 mg/kg of body weight.
2. The method of claim 1 , wherein the CysC fusion polypeptide consists of the amino acid sequence of SEQ ID NO:6.
3. A method for lowering both Abeta plaque and hyperphosphorylated Tau tangle plaque in a brain of a subject suffering from Alzheimer's disease (AD) compared to the Abeta plaque and hyperphosphorylated Tau tangle plaque in the brain of the subject suffering from AD with no treatment, comprising administering to the subject suffering from AD an isolated polypeptide consisting of the amino acid sequence of SEQ ID NO:6.
4. The method of claim 3 , wherein the polypeptide is administered to the subject at a dose of about 1 to 10 mg/Kg of body weight.