Method of modulating the concentration of proteins in cerebrospinal fluid

A method of treating age-related loss in brain function, the method comprising:

• measuring a concentration of a protein selected from the group consisting of tau, phosphorylated tau (P-tau), β-amyloid, neurofilament light (NF-L), total α-synuclein, and neurogranin in the cerebrospinal fluid of a patient suffering from age related cognitive decline in the absence of clinical signs of dementia, wherein the patient is at most 50 years of age, and the β-amyloid is a 39-43 amino acid amyloid β protein (Aβ) secreted as Aβ39, Aβ40, Aβ42, or Aβ43;
• comparing the measured concentrations of the protein to a median concentration of the protein in a reference cognitively normal population to determine if the patient is susceptible from suffering from age related cognitive decline in the absence of clinical signs of dementia;
• administering an effective dose of a gonadotropin-releasing hormone (GnRH) analog to the patient:
• if the concentrations of tau, P-tau, neurofilament light (NF-L), total α-synuclein, or neurogranin are above a lower quartile of the reference cognitively normal population;
• or
• if the concentration of β-amyloid is below an upper most quartile of the reference cognitively normal population.

A method of preventing age-related loss of brain function, the method comprising:

• measuring a concentration of a protein selected from the group consisting of tau, phosphorylated tau (P-tau), β-amyloid, neurofilament light (NF-L), total α-synuclein;
• and neurogranin in the cerebrospinal fluid of a patient susceptible to suffering from age related cognitive decline in the absence of clinical signs of dementia, wherein the patient is at most 50 years of age, and the β-amyloid is a 39-43 amino acid amyloid β protein (Aβ) secreted as Aβ39, Aβ40, Aβ42, or Aβ43;
• comparing the measured concentrations of the protein to a median concentration of the protein in a reference cognitively normal population to determine if the patient is susceptible from suffering from age related cognitive decline in the absence of clinical signs of dementia;
• administering an effective dose of a gonadotropin-releasing hormone (GnRH) analog to the patient:
• if the concentrations of tau, P-tau, neurofilament light (NF-L), total α-synuclein, or neurogranin are above a lower quartile of the reference cognitively normal population;
• or
• if the concentration of β-amyloid is below an upper most quartile of the reference cognitively normal population.

A method of preventing age-related loss in brain function in a post-menopausal patient with leuprolide, the method comprising:

• measuring a concentration of a protein selected from the group consisting of tau, phosphorylated tau (P-tau), β-amyloid, neurofilament light, total α-synuclein, and neurogranin in the cerebrospinal fluid of the patient, wherein the patient is neurologically normal and is at most 50 years of age, and wherein the 3-amyloid is a 39-43 amino acid amyloid β protein (Aβ) secreted as Aβ39, Aβ40, Aβ42, or Aβ43;
• comparing the measured concentrations of the protein to a median concentration of a reference cognitively normal population to determine if the patient is susceptible from suffering from age related cognitive decline in the absence of clinical signs of dementia;
• administering an effective dose of leuprolide to the patient:
• if the concentrations of tau, P-tau, neurofilament light, total α-synuclein, or neurogranin are above a lower quartile of the reference cognitively normal population;
• or if the concentration of β-amyloid is below an upper most quartile of the reference cognitively normal population or lower than the median concentration of the reference cognitively normal population;
• wherein the effective dose of leuprolide is from 0.2 to 20 mg/day, 1 to 10 mg/month, or 10 to 50 mg every three months.