Methods and means for stratification of an individual suffering from, or suspected to suffer from, a progressive neurodegenerative disease

A method of treating a patient comprising administering a β-secretase inhibitor, an immune-modulating agent, an anti-tau and/or anti-beta amyloid antibody, a block copolymer and/or a corticosteroid to the patient suffering from a progressive neurodegenerative disease, comprising the steps of:

• (a)—subtyping a sample of a patient suffering from a progressive neurodegenerative disease, comprising the steps of:
• (a1)—providing a sample from the patient, whereby the sample comprises gene expression products of said patient;
• (a2)—determining a level of expression for at least three gene expression products listed in Table 2, wherein said at least three gene expression products listed in Table 2 comprise CHGA, MASP1, and PLG;
• (a3)—comparing said determined levels of expression of each of the at least three gene expression products to a reference level of expression of each of the three gene expression products in a reference sample;
• and
• (a4)—identifying a disease subtype, wherein the disease subtype is in a hyperplastic subgroup, a neuroinflammation subgroup or a BBB dysfunction subgroup, by comparison of the determined levels of expression level and the level of expression in a reference sample, thereby requiring treatment according to step (b);
• and
• (b) administering a β-secretase inhibitor when the patient is subtyped in a hyperplastic subgroup, administering an immune-modulating agent when the patient is subtyped in a neuroinflammation subgroup, and administering an anti-tau and/or anti-beta amyloid antibody or a block copolymer and/or a corticosteroid when the patient is subtyped in the BBB dysfunction subgroup,
• wherein the immune-modulating agent is PD-1, PD-L1 and/or CTLA-4 targeting antibodies, and/or p38 MAPK inhibitors,
• wherein the block copolymer is poly(ethylene oxide) and/or poly(propylene oxide), and
• wherein the corticosteroid is dexamethasone, methylprednisolone, prednisone, prednisolone, cortisol, cortisone, betamethasone, triamcinolone, fludrocortisone acetate and/or deoxycorticosterone acetate.