Rejuvenated Blood Cells Restore Memory and Brain Health in Alzheimer’s Mice todayheadline

Hope for aging brains may come from our own blood. Researchers at Cedars-Sinai Medical Center show that immune cells derived from human induced pluripotent stem cells (iPSCs) can restore memory, reduce inflammation, and rejuvenate neural health in mouse models of aging and Alzheimer’s disease. Published in Advanced Science, the study finds that intravenous injections of these mononuclear phagocytes, called iMPs, improve hippocampus-dependent cognition without ever entering the brain. Instead, the cells act through peripheral signals that ripple inward.

Young Blood Without the Donor

For years, young plasma transfusions and bone marrow transplants hinted at ways to roll back age-related decline, but both approaches were impractical. Limited supply, invasive procedures, and immune risks kept them far from clinic. The Cedars-Sinai team tried a different route: generating fresh mononuclear phagocytes from reprogrammed stem cells. These white blood cells normally clear debris and dampen inflammation but falter with age. Rejuvenated iMPs, the researchers hypothesized, might reset the system.

“Short-term intravenous treatments with iPSC-derived mononuclear phagocytes improve cognitive decline and neural health in two mouse models of aging and in the 5xFAD mouse model of Alzheimer’s disease.”

Better Memory, Healthier Cells

Mice received repeated doses of iMPs over three weeks. Aging mice treated with saline stumbled on spatial memory tasks, while their iMP-treated peers performed like the young. The treatment restored hippocampal mossy cells, neurons central to novelty and context memory. Microglia, the brain’s sentinels, regained branching complexity and dropped markers of hyperactivation. Importantly, female mice showed subtler benefits but still saw improvements in microglial health.

Single-nucleus RNA sequencing told the same story: iMPs reduced the transcriptional “age” of nine hippocampal cell types, including mossy cells and microglia. Proteomic analysis of plasma revealed another clue—iMPs reversed age-related increases in serum amyloid proteins SAA2 and SAP, molecules tied to neurodegeneration and dementia risk. In lab dishes, iMP-conditioned media shielded human microglia from amyloid-induced death. The cells weren’t entering the brain, but their signals were felt there.

Alzheimer’s Model Put to the Test

To push the system harder, the researchers treated 5xFAD mice, a standard Alzheimer’s model that develops early amyloid pathology. In young 5xFAD mice, iMPs improved recognition memory. In older ones, they rescued spatial location memory. Amyloid plaques remained unchanged, but cognition improved anyway. As the authors note, amyloid levels and cognitive health often fail to correlate. The benefits instead tracked with restored mossy cells and healthier microglia.

“iMP treatment improves recognition and location memory in young and aging 5xFAD mice, respectively, and increases microglial branch length and mossy cells in aging 5xFAD mice.”

A Peripheral Fix for a Central Problem

The striking part: iMPs never breached the blood-brain barrier. They lodged in peripheral organs like the lung and spleen, secreting factors that reshaped systemic signals. This peripheral-to-central crosstalk echoes findings from young plasma experiments and raises the possibility of a safer, more scalable therapy. Because iPSCs can be derived from a patient’s own cells, iMPs could in theory offer personalized treatment without immune rejection.

Questions remain. Would longer dosing regimens amplify the effects? Could specific proteins secreted by iMPs be identified as the therapeutic drivers? And will these results in mice translate to human neurodegeneration, where timelines stretch across decades rather than weeks? Still, the findings suggest that protecting aging brains may not require invasive brain cell replacement. Sometimes it is enough to restore balance at the body’s edges.

Advanced Science, DOI: 10.1002/advs.202417848

The takeaway is simple, if startling: rejuvenated immune cells, generated from stem cells, can restore memory in aging and Alzheimer’s mice—not by going into the brain, but by changing the signals that reach it.