ALSENLITE: Senolytics for Alzheimer's Disease

1. Men and women of age 55 years and older at the time of enrollment

2. Clinical diagnosis of symptomatic probable AD (MMSE 26 to 15 or Short Test of Mental Status 31 to 15 inclusive and/or Clinical Dementia Rating Scale/CDR = 0.5 to 2, inclusive)

3. Not on cholinesterase inhibitors or memantine; or if on cholinesterase inhibitors and/or memantine, on a stable dose for at least three months

4. Body Mass Index (BMI) within range of 19 - 50 kg/ m2

5. Participants must be accompanied by a LAR designated to sign informed consent and to provide study partner reported outcomes at all visits

6. Participants must have no plans to travel over the ~3 months between Visits 3 and 14 that interfere with study visits

7. Tau positivity by brain PET imaging

8. Adequate blood counts i.e. platelets > 50,000 per microliter; HB > 9/dL, and ANC > 1000 per microliter

9. Availability and consent from a LAR

1. Unwilling or unable to give informed consent

2. Pregnancy

3. QTc > 450 msec on baseline ECG

4. MRI contraindications

5. Presence of uncontrolled psychiatric disorder (as per clinical judgment)

6. Presence of uncontrolled systemic lupus erythematosus (as per clinical judgment)

7. Substance or alcohol abuse (current alcohol use > 3 alcoholic beverage/day or > 21 per week and as per clinical judgment)

8. Hearing, vision, or motor deficits despite corrective devices (as per clinical judgment)

9. Myocardial infarction, angina, stroke, or transient ischemic attack in the past 6 months

10. Chronic heart failure (as per clinical judgment)

11. Neurologic, musculoskeletal, or other condition that limits subject's ability to complete study physical assessments (as per clinical judgment)

12. Positive SARS-CoV-2 test within 30 days prior to enrollment

13. AST/ALT > 2.5x upper limit normal

14. Presence of significant liver disease with total bilirubin > 2X upper limit or as per clinical judgment

15. Inability to tolerate oral medication (as per clinical judgment)

16. Abnormality in any of the screening laboratory studies (see section 6.21.2) or as per clinical judgment

17. Malabsorption (as per clinical judgment)

18. Known human immunodeficiency virus infection (as per clinical judgment)

19. Known active hepatitis B or C infection

20. Invasive fungal or viral infection (as per clinical judgment)

21. Known hypersensitivity or allergy to D or Q

22. Uncontrolled pleural/pericardial effusions or ascites (as per clinical judgment)

23. New/active invasive cancer except non-melanoma skin cancers

24. Inability to tolerate oral medications (as per clinical judgment)

25. Currently taking AND unable to safely hold any of the medications listed in Appendix 1 during the days IP is administered and for 36 hours after IP administration.

26. Uncontrolled diabetes (defined as HbA1c > 7% or as per clinical judgment).

27. Gastric bypass/reduction

28. Crohn's disease

29. Myopathies (increased or low calcium, vitamin D deficiency, elevated creatine kinase or ESR) (as per clinical judgment)

30. eGFR < 10 ml/ min/ 1.73 m2

31. Creatinine clearance < 60 mL/min/1.73 m2

32. Subjects on therapeutic doses of anticoagulants (e.g., warfarin, heparin, low molecular weight heparin, factor Xa inhibitors, etc.)

33. On antiplatelet agents (e.g., full dose Aspirin, Clopidogrel etc.). Baby aspirin (81 mg), if absolutely necessary from cardiac perspective, will be allowed

34. Presence of any condition that the Investigator believes would put the subject at risk or would preclude the patient from successfully completing all aspects of the trial

Involvement of special vulnerable populations: We will not involve special vulnerable populations, such as fetuses, neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations except for patients with dementia. Therefore, availability and consent from a LAR is an inclusion criterion.