Key Takeaways

• Fat cells in bone marrow that become senescent—non-dividing, aged cells—release a molecule called SAP.
• SAP supports the buildup of Alzheimer’s–associated amyloid-beta proteins in bone, and senolytic treatments (which remove senescent cells) help prevent age-related bone loss.
• These findings suggest a dual potential therapy: targeting both Alzheimer’s dementia and osteoporosis with the same senolytic approach.

A Fresh Perspective on Alzheimer’s

Alzheimer’s has long been viewed mainly as a brain-centric disease marked by amyloid-beta buildup. But a recent study in Nature Aging by Johns Hopkins researchers expands this view—demonstrating that amyloid-beta also accumulates in bones.

“Almost nothing is known about whether amyloid forms in the skeleton or how it might contribute to age-related bone loss,” notes Mei Wan, PhD, co-author of the study.

Senescence: The Hidden Culprit in Bones

• In aging bone marrow, fat cells increase in number and many enter a senescent state—a process where stressed cells stop dividing but start secreting harmful substances.
• These senescent fat cells are found surrounded by amyloid-beta deposits in older mice—but not in younger ones—linking them directly to pathological protein accumulation.
• A key discovery: these cells secrete SAP (serum amyloid P component), which stabilizes amyloid fibrils and promotes their aggregation.

Reversing Bone Decline Through Targeted Interventions

• Transplant experiments: Young mice transplanted with bone fat cells from old mice experienced bone loss—but this was prevented with senolytics (particularly a combo of dasatinib and quercetin, or “DQ”).
• Removing SAP with a drug called miridesap cleared amyloid deposits and restored bone mass in older mice.
• Further research revealed SAP combined with amyloid-beta shifts bone balance—boosting osteoclasts (which break down bone) while suppressing osteoblasts (which build bone), leading to bone loss.

Potential Treatment Synergies: Alzheimer’s and Osteoporosis

• Observed trends: Low bone mineral density correlates with a higher Alzheimer’s risk, and bone loss often appears in early Alzheimer’s—suggesting a shared pathological thread
• Excitingly, senolytic therapies may serve both conditions:
  • A clinical trial established that dasatinib + quercetin (DQ) is safe in early-stage Alzheimer’s patients.
  • In a phase 2 trial, DQ increased bone formation markers in older women, indicating benefits against osteoporosis.
• Future studies will test whether senolytics like DQ (and others, such as fisetin) can prevent or reverse both Alzheimer’s-related brain effects and bone loss, especially if administered early.

Summary Table

Final Thoughts

This Johns Hopkins study uncovers a compelling new link between dementia risk and bone health—namely, the role of senescent bone fat cells and SAP in promoting amyloid-beta buildup and bone loss.

The implications are powerful: targeting these senescent cells may not only improve bone health but also support neurological function—potentially offering a dual therapeutic strategy against two major age-related conditions.