Therapeutic strategies for prevention and treatment of alzheimer's disease

1. A method of selecting a candidate compound for use in the treatment of Alzheimer's disease in a human patient, which method comprises:

(a) incubating proliferating lymphocytes of said patient in the presence of one or more pharmaceutical agent(s), wherein said proliferating lymphocytes exhibit a cell cycle regulatory defect at the G1/S phase transition and wherein said pharmaceutical agent(s) are:

i) inhibitors of cell cycle re-entry or progression to the G1/S transition; or

ii) inhibitors of progression of the cell cycle through the G1/S transition point; and

(b) screening and selecting a compound that corrects said regulatory defect at the G1/S transition in said proliferating lymphocytes as a candidate compound for use in the treatment of Alzheimer's disease in said patient.

2. The method according to claim 1 , wherein said one or more pharmaceutical agent(s) include(s):

(A) one or more inhibitors of cell cycle re-entry or progression to the G1/S transition that is an inhibitor of the G0/G1 transition, or

(B) one or more inhibitors of progression of the cell cycle through the G1/S transition point that blocks cell cycle progression in G1, induces cell cycle arrest in G1, induces cell cycle arrest at the G1/S checkpoint, blocks the G1/S transition or inhibits DNA synthesis.

3. The method according to claim 2 , wherein said one or more pharmaceutical agent(s) include(s) sodium valproate.

4. The method according to claim 2 , wherein said one or more pharmaceutical agent(s) include(s) a retinoid or retinoid receptor selective ligand, an ansamycin, a vitamin D analogue, a steroid or glucocorticoid, or an alpha adrenergic receptor antagonist.

5. The method according to claim 1 , wherein the pharmaceutical agent is an inhibitor of the G0/G1 transition.

6. The method according to claim 1 , wherein the pharmaceutical agent induces cell cycle arrest in the G0/G1 phase.

7. The method according to claim 1 , wherein the pharmaceutical agent is sodium valproate.

8. The method according to claim 1 , wherein the pharmaceutical agent blocks cell cycle progression in G1.

9. The method according to claim 1 , wherein the pharmaceutical agent induces cell cycle arrest in G1.

10. The method according to claim 1 , wherein the pharmaceutical agent induces cell cycle arrest at the G1/S checkpoint.

11. The method according to claim 1 , wherein the pharmaceutical agent blocks the G1/S transition.

12. The method according to claim 1 , wherein the pharmaceutical agent inhibits DNA synthesis.

13. The method according to claim 1 , wherein the pharmaceutical agent is:

(a) a retinoid or retinoid receptor selective ligand;

(b) an ansamycin;

(c) a steroid or glucocorticoid; or

(d) an alpha adrenergic receptor antagonist.

14. The method according to claim 13 , wherein the candidate pharmaceutical agent is alpha adrenergic receptor antagonist, and wherein said alpha adrenergic receptor antagonist is doxazosin.