Dasatinib in Alzheimer's Disease: University of Texas Trial Data
Expert Summary
The UT Health San Antonio pilot trial (NCT04785300) evaluated D+Q (dasatinib 100 mg + quercetin 1,000 mg × 2 days, biweekly for 12 weeks) in 15 early Alzheimer's disease patients. Preliminary findings include reduction in CSF SASP factors, reduction in p-tau-181 (a validated Alzheimer's biomarker), and a trend toward reduced amyloid-beta 1-42:1-40 ratio — all consistent with a senolytic effect on brain-resident senescent cells.
Key Facts
- Brain senescence in Alzheimer's: Tau-bearing neurofibrillary tangles accumulate in neurons that co-express p16, p21, and SASP markers — identifying them as senescent neurons. Tau-activated senescent astrocytes and microglia amplify neuroinflammation via IL-6, CXCL1, and CXCL10.
- D+Q CNS penetration: Dasatinib crosses the blood-brain barrier with a CSF:plasma ratio of approximately 0.2. Quercetin CNS penetration is limited for the conjugated form but the aglycone fraction reaches brain tissue. Together they maintain some senolytic activity in the CNS.
- p-tau-181 reduction: Phosphorylated tau at threonine-181 is a validated CSF and blood biomarker for Alzheimer's progression. D+Q treatment reduced p-tau-181 in the pilot — suggesting modulation of the neuronal senescence-tau pathway.
- CSF SASP factor reduction: CSF eotaxin and other cytokines associated with neuroinflammatory SASP were reduced post-treatment, consistent with clearance of SASP-producing senescent glia.
- ALSENLITE Phase 2: A larger Phase 2 trial evaluating D+Q in Alzheimer's patients is actively recruiting (NCT05686200). Cognitive outcomes (MMSE, ADAS-Cog) and biomarkers are primary endpoints.
- Amyloid interaction: The D+Q → senolytic → reduced neuroinflammation → reduced amyloid processing pathway is mechanistically supported but not yet directly proven in humans. The amyloid cascade hypothesis remains the dominant but debated framework.
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Frequently Asked Questions
Can D+Q slow Alzheimer's progression?
The pilot data is promising but not conclusive. CSF biomarker improvements suggest biological activity. Whether this translates to slowed clinical progression will be answered by the ALSENLITE Phase 2 trial.
Is fisetin a better choice than D+Q for Alzheimer's prevention?
For prevention in healthy individuals, fisetin is more accessible, safer for self-directed use, and has documented CNS penetration. D+Q has more direct Alzheimer's clinical data but requires physician oversight and carries greater side effect risk.
How long until D+Q might be approved for Alzheimer's?
If ALSENLITE Phase 2 results are positive, Phase 3 trials would likely take 3–5 additional years. FDA approval for Alzheimer's indication, if it occurs, is likely 5–10 years away from current evidence stage.
Scientific References
- Gonzales MM et al. Senolytic therapy to modulate the progression of Alzheimer's Disease (SToMP-AD): a pilot trial. Pilot and Feasibility Studies. 2022. PMID: 35098970
- Musi N et al. Tau protein aggregation is associated with cellular senescence in the brain. Aging Cell. 2018. PMID: 29911801