Damage to the bone marrow triggered by Alzheimer’s disease may explain why the body’s immune system is unable to restore brain health in the neurodegenerative condition, a new study suggests.
For decades, Alzheimer’s disease research has focused on the role played by misfolded proteins in the brain, including amyloid-beta plaques and tangled tau proteins.
But some of the most significant damage in the condition may be caused far away from the brain, in the spongy bone marrow tissue.
The bone marrow is home to the body’s stem cells, which play a major role in giving rise to specialised immune cells and helping heal damaged tissue.
Previous studies have hinted that special immune cells from the bone marrow act as reinforcements for the brain’s resident immune cells in helping fight Alzheimer’s pathology.
As the resident cells become exhausted and lose their ability to clear amyloid plaques efficiently, they can reduce inflammation and slow cognitive decline, according to earlier research in mice.
But exactly which immune cells these are and how they travel to the brain has remained unclear.
“The factors limiting their spontaneous homing to the diseased brain remain unclear,” researchers wrote in the study published in the journal Nature Neuroscience.
Scientists found that the immune cells’ monocytes are the ones impaired in Alzheimer’s disease.
“In this study, we discovered that monocyte development is impaired in mouse models and in patients,” scientists wrote.
Researchers also found in mice that the Alzheimer’s condition disrupts an immune system alarm signal that enables the bone marrow to send monocyte reinforcements to the brain.
In healthy mice, scientists found that a large fraction of bone marrow stem cells are capable of replenishing the immune system over the long term.
However, in mice with Alzheimer’s, this ability was lost.
The bone marrow stem cells in the mice matured much earlier into special cells, and the process that generates monocytes was found to be visibly impaired.
Something similar was also seen in human Alzheimer’s patients, researchers say.
“A similar phenotype was found in circulating monocytes from patients with AD,” they wrote.
When scientists restored the bone marrow process behind monocyte production with a targeted therapy, it “ameliorated disease pathology”, they found.
“This was accompanied by increased homing of monocyte-derived macrophages to the brain,” scientists wrote.
In Alzheimer’s patients, researchers suspect that the self-renewal capacity of stem cells is exhausted early, showing signs of accelerated ageing of the blood system.
The findings add to a growing body of recent studies proving that Alzheimer’s disease is not just a brain condition but an overall systemic, body-wide condition.
However, since the research was largely conducted in mice, scientists caution that more studies are needed to translate the findings into therapies for humans.
