Screening method

A method of improving the accuracy of a screen for the presence of a cell cycle regulatory defect associated with Alzheimer's disease in a human subject, wherein the method comprises the steps of:

• i) obtaining a sample from the human subject;
• ii) detecting the presence of a cell cycle regulatory defect at the G1/S phase transition in at least one non-neuronal cell from the sample obtained from the human subject in step i), wherein said detecting for the presence of a cell cycle regulatory defect at the G1/S phase transition is carried out by:
• inducing cell division in the non-neuronal cell or cells from the sample from the human subject and testing the responsiveness of the cell or cells to a cell division inhibitor substance, wherein a reduced responsiveness to the cell division inhibitor substance in the cell or cells from the sample of the human subject, as compared to control cells not having a cell cycle regulatory defect at the G1/S phase transition, is an indication of the presence of a cell cycle regulatory defect at the G1/S phase transition;
• and
• iii) detecting the presence of the apoE4 genotype from cells of the sample of the same human subject of step i),
• wherein the result of step iii) and the result of step ii) are entered as variables into a diagnostic predictor equation in order to derive a probability value that is improved in comparison to the result obtained in step ii),
• wherein the diagnostic predictor equation has coefficients obtained by performing steps (i)-(iii) on a population of test human subjects and combining the results obtained by performing steps (i)-(iii) on a population of test human subjects by logistic regression.

A method of determining the risk of developing Alzheimer's disease in a human subject, wherein the method comprises the steps of:

• i) obtaining a sample from the human subject;
• ii) detecting the presence of a cell cycle regulatory defect at the G1/S phase transition in at least one non-neuronal cell from the sample obtained from the human subject in step i), wherein said detecting for the presence of a cell cycle regulatory defect at the G1/S phase transition is carried out by:
• inducing cell division in the non-neuronal cell or cells from the sample from the human subject and testing the responsiveness of the cell or cells to a cell division inhibitor substance, wherein a reduced responsiveness to the cell division inhibitor substance in the cell or cells from the sample of the human subject, as compared to control cells not having a cell cycle regulatory defect at the G1/S phase transition, is an indication of the presence of a cell cycle regulatory defect at the G1/S phase transition;
• and
• iii) detecting the presence of the apoE4 genotype from cells of the sample of the same human subject of step i),
• wherein the result of step iii) and the result of in step ii), are entered as variables into a diagnostic predictor equation in order to derive a probability value for the human subject's risk of developing Alzheimer's disease,
• wherein the diagnostic predictor equation has coefficients obtained by performing steps (i)-(iii) on a population of test human subjects and combining the results obtained by performing steps (i)-(iii) on a population of test human subjects by logistic regression.

A method to assist with clinical diagnosis of Alzheimer's disease in a live human subject, wherein the method comprises the steps of:

• i) obtaining a sample from the live human subject;
• ii) detecting the presence of a cell cycle regulatory defect at the G1/S phase transition in at least one non-neuronal cell from the sample obtained from the live human subject in step i), wherein said detecting for the presence of a cell cycle regulatory defect at the G1/S phase transition is carried out by:
• inducing cell division in the non-neuronal cell or cells from the sample from the live human subject and testing the responsiveness of the cell or cells to a cell division inhibitor substance, wherein a reduced responsiveness to the cell division inhibitor substance in the cell or cells from the sample of the live human subject, as compared to control cells not having a cell cycle regulatory defect at the G1/S phase transition, is an indication of the presence of a cell cycle regulatory defect at the G1/S phase transition;
• and
• iii) detecting the presence of the apoE4 genotype from cells of the sample of the same live human subject of step i),
• wherein the result of step iii) and the result of step ii) are entered as variables into a diagnostic predictor equation in order to derive a probability value that is indicative of the subject having Alzheimer's disease,
• wherein the diagnostic predictor equation has coefficients obtained by performing steps (i)-(iii) on a population of test human subjects and combining the results obtained by performing steps (i)-(iii) on a population of test human subjects by logistic regression.

A method for assessing the efficacy of a candidate therapy for the treatment of Alzheimer's disease in a human subject recipient of such therapy, wherein the method comprises the steps of:

• i) obtaining a sample from the human subject;
• ii) detecting the extent of a cell cycle regulatory defect at the G1/S phase transition in at least one non-neuronal cell from the sample obtained from said human subject in step i), wherein said detecting the extent of a cell cycle regulatory defect at the G1/S phase transition is carried out by:
• inducing cell division in the non-neuronal cell or cells from the sample from the human subject and testing the responsiveness of the cell or cells to a cell division inhibitor substance, wherein a reduced responsiveness to the cell division inhibitor substance in the cell or cells from the sample of the human subject, as compared to control cells not having a cell cycle regulatory defect at the G1/S phase transition, is an indication of the extent of a cell cycle regulatory defect at the G1/S phase transition;
• and
• iii) detecting the presence of the apoE4 genotype from cells of the sample of the same human subject of step i),
• wherein the result of step iii) and the result of step ii) are entered as variables into a diagnostic predictor equation in order to derive a probability value that is indicative of a diagnostic criterion associated with the efficacy of said candidate therapy for the treatment of Alzheimer's disease
• wherein the diagnostic predictor equation has coefficients obtained by performing steps (i)-(iii) on a population of test human subjects and combining the results obtained by performing steps (i)-(iii) on a population of test human subjects by logistic regression.

A method of determining a prognostic criterion that is indicative of the rate of cognitive decline due to Alzheimer's Disease in a human subject, wherein the method comprises the steps of:

• i) obtaining a sample from the human subject;
• ii) detecting the presence of or the extent of a cell cycle regulatory defect at the G1/S phase transition in at least one non-neuronal cell from the sample obtained from the human subject in step i), wherein said detecting the presence or extent of a cell cycle regulatory defect at the G1/S phase transition is carried out by:
• inducing cell division in the non-neuronal cell or cells from the sample from the human subject and testing the responsiveness of the cell or cells to a cell division inhibitor substance, wherein a reduced responsiveness to the cell division inhibitor substance in the cell or cells from the sample of the human subject, as compared to control cells not having a cell cycle regulatory defect at the G1/S phase transition, is an indication of the extent of a cell cycle regulatory defect at the G1/S phase transition;
• and
• iii) detecting the presence of the apoE4 genotype from cells of the sample of the same human subject of step i),
• wherein the result of step iii) and the result of step ii) are entered as variables into a diagnostic predictor equation in order to derive a probability value that is indicative of the prognostic criterion indicative of the rate of cognitive decline due to Alzheimer's disease in the human subject
• wherein the diagnostic predictor equation has coefficients obtained by performing steps (i)-(iii) on a population of test human subjects and combining the results obtained by performing steps (i)-(iii) on a population of test human subjects by logistic regression.