Young bone marrow transplants may help fight Alzheimer’s, mouse study…

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Bone marrow contains stem cells that make the many types of blood cell our immune system needs.
The diversity of these blood cells drops as we age, and this is thought to contribute to some aspects of aging.
Researchers in China gave bone marrow transplants to older mouse models of Alzheimer’s disease from younger mouse models, and found that the transplants reversed some signs of aging and amyloid-beta accumulation.
It also improved cognition in the mice.
Mice that received bone marrow transplants from younger mice as part of a recent study had lower levels of many signs of brain aging.
Not only did they have lower levels of neuronal degeneration, they also had fewer behavioral deficits and lower levels of amyloid-beta, the peptide that characterizes Alzheimer’s disease, in their brains.
Alzheimer’s disease
Researchers from the Third Military Medical University, Chongqing, China hypothesized that younger hematopoietic stem cells, the stem cells in the bone marrow that make different types of blood cells, could help to counter some of the signs of aging, when transplanted into older mice.
Their results appear in Science Advances.
Science Advances
Why might bone marrow transplants help in Alzheimer’s?
The researchers decided to explore this avenue because previous studies had shown that, as people age, the diversity of their hematopoietic — blood cell-generating — stem cells drops, through a mechanism known as clonal hematopoiesis.
previous studies
clonal hematopoiesis
Stem cells with mutations that drive proliferation dominate the stem cell population, thus reducing its overall diversity.
This has a particular effect on the diversity of the immune cells the body can produce, and some researchers believe it may be one of the reasons why older people become less likely to be able to stave off infection.
In this instance, the researchers looked at the effect of bone marrow transplants on the brain and Alzheimer’s disease markers.
This was pertinent as Alzheimer’s disease is a disease of aging, Rizwan Bashir, MD, a neurologist at Acia Orthopedics, and not involved in the current research, told Medical News Today.
Rizwan Bashir, MD
He explained:
“Alzheimer’s disease is predominantly a disease of aging because it is strongly associated with the biological changes that occur as we grow older. As we age, there is a natural decline in brain function due to the accumulation of cellular damage, oxidative stress, and reduced efficiency in clearing metabolic waste.“
“This progressive decline can lead to the buildup of amyloid beta plaques and tau tangles, which are hallmark features of Alzheimer’s disease. Moreover, the brain’s ability to repair itself diminishes with age, making it more susceptible to neurodegenerative processes,” he continued.
Bone marrow transplants to counter brain aging?
To investigate the relationship between age of hematopoietic stem cells and brain aging, and whether or not a bone marrow transplant can restore them, researchers used 9- and 2-month-old mice that had been genetically engineered to model Alzheimer’s disease.
They made two groups of 9 month old mice, and gave one group bone marrow transplants from 2 month old mice, and a control group bone marrow transplants from other, 9 month old mice.
They first compared the expression of genes in older and younger mice, and identified a number of age-related genes that were either up or down-regulated in the older mice.
Up-regulated aging pathways identified in the older mice were commonly associated with mitochondrial function, and down-regulated aging pathways were commonly associated with epigenetic regulation and immune processes.
Dysfunctions in mitochondria, the so-called powerhouses of the cell, have been associated with Alzheimer’s disease, as have certain epigenetic changes, which are changes in gene expression triggered by a person’s environments and lifestyle factors.
mitochondria
associated with Alzheimer’s
epigenetic changes
Ultimately, researchers found the expression of these genes was restored after bone marrow transplant. T-cells and monocytes, two types of immune cells, were most affected by the bone marrow transplant.
Researchers also compared the expression of the top 45 Alzheimer’s disease risk genes in the different types of immune cell.
They found that the top 10 Alzheimer’s disease risk genes were differentially expressed in a type of white blood cell called monocytes in older mice, and young bone marrow transplant reversed these expression changes.
In particular, bone marrow transplant restored the ability of monocytes to eliminate amyloid-beta build up, reducing cerebral and plasma amyloid-beta levels in the 9-month-old mice that had received a bone marrow transplant with the bone marrow of younger mice.
These mice also displayed lower neuroinflammation (brain inflammation) and neuronal (brain cell) loss. Furthermore, behavior relating to cognition improved in the older mice following bone marrow transplant.
What are the ethical concerns?
Zachary Harvanek, MD, PhD, instructor of psychiatry at Yale, who researches aging and was not involved in the research told MNT that the bone marrow transplant appeared to be having an effect on the whole body.
Zachary Harvanek, MD, PhD
“It seems the young bone marrow transplant is improving the function of the immune system both systemically and in the brain. The immune system appears to play an important role in clearing the plaques in the brain which are hallmarks of Alzheimer’s disease, and this study suggests that a bone marrow transplant might help clear these plaques by rejuvenating the immune system,” he noted.
Attempting to translate the procedure to humans was fraught with ethical problems, Harvanek cautioned, noting that, “[w]ith what we know now, performing bone marrow transplants on otherwise healthy humans to investigate the prevention of aging-related diseases is far too risky.“
“The use of young, allogenic donors for proposed interventions on aging such as heterochronic parabiosis or bone marrow transplants, would be fraught with ethical concerns regarding equity and exploitation, conjuring up dystopian future images of billionaire ‘vampires’ obtaining young blood or bone marrow to keep themselves young,“ said the researcher.
“One way to avoid this would be to use heterochronic autologous transplants, that is, taking your blood or bone marrow from an earlier age and then transplanting it back into yourself, which might show similar effects. However, if research can identify the specific aspects of these transplants that affects the aging process — for example, serum blood proteins seem to be important in heterochronic parabiosis — then the benefits might be obtained without a transplant at all. In both of these scenarios the risk of exploitation would be diminished, though there would still be important ethical concerns regarding access to treatment.”
– Zachary Harvanek, MD, PhD
Still, though there were risks, bone marrow transplants were a well defined, ultimately safe treatment for the people who needed them to treat illness, Harvanek admitted.