Affiliations: [a] Department of Internal Medicine Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA
| [b] Salisbury VA Medical Center, Salisbury, NC, USA
Correspondence:
[*]
Correspondence to: Miranda E. Orr, PhD, Department of Internal Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. Tel.: +1 336 716 7804; E-mail: [email protected].
Abstract: Cellular senescence contributes to Alzheimer’s disease (AD) pathogenesis. Treatments that remove senescent cells, senolytics, improve brain outcomes in AD mice with amyloid-β or tau deposition. 3xTgAD mice develop both AD neuropathologies; however, Ng et al. report low p16INK4a-associated senescence in the brain. Senolytic treatment by genetic removal; dasatinib with quercetin (D+Q), which enter the brain; and ABT-263 with limited brain penetrance all reduced AD neuropathology. Refined measures of senescence and brain exposure would help clarify the benefits of senolytics despite low p16INK4a-associated senescence and potential limited brain penetrance.
