Stem cell transplants deliver promising treatments for mice with Alzheimer’s disease – Courthouse News Service
Posted: June 1, 2024 at 2:47 am
A potential therapy for Alzheimer's disease highlights the important role of the immune system and how stem cell transplants can help revitalize aging cells linked to the neurodegenerative disease in mice.
(CN) Scientists on Tuesday revealed how young bone marrow stem cell transplants could be the future of treating immune cells that assist with the progression of Alzheimers Disease.
The findings in Science Advances come from a team of Chinese researchers who successfully transplanted bone marrow from two-month-old mice to restore the immune systems of their older counterparts affected by genetic and pathological indicators of Alzheimers disease.
Alzheimers is a progressive and fatal neurological disease that commonly affects people over the age of 65. Prevailing Alzheimers research links the disease to the buildup of amyloid beta and tau proteins in the brain, though other recent studies have found that approximately half of the genes associated with Alzheimer's are directly involved with the immune system.
As the researchers explain in the study, aged immune systems undergo immunosenescence the gradual decline of immune cell production and functionality which partly derives from aging bone marrow hematopoietic stem cells and progenitor cells.
Progenitor cells develop or differentiate into a predetermined type of cell. Hematopoietic stem cells are the source of peripheral immune cells like monocytes, macrophages and dendritic cells all of which can assist in the progression of neurodegenerative and neuroinflammatory diseases when they reach the brain.
The process of immunosenescence thus drives systemic aging and contributes to an increased susceptibility to age-related diseases like Alzheimer's disease. Using this information, the team realized that replenishing bone marrow with young hematopoietic stem cells can rejuvenate older immune cells and intervene in Alzheimers symptoms.
And thats not all they found.
Our findings revealed that aging induced changes in the gene expression in both innate and adaptive immune cells, aligned with the dysfunction of both innate and adaptive immune responses observed in aging animals or elderly individuals, such as diminished phagocytosis function of monocytes, impaired antiviral immunity of [natural killer] cells, elevated production of autoantibodies by B cells and expansion of cytotoxic T cells, the authors wrote.
The team also found that the genetic markers associated with aging were enriched for Alzheimers-related pathways, indicating an active link between senescent or deteriorating peripheral immune cells and the development of Alzheimer's especially monocytes.
Monocytes are a type of white blood cell that can clear amyloid beta proteins in the brain and plasma through phagocytosis (kind of like a cellular version of Pac-Man). Aging, however, can impair this ability and accelerate the occurrence of Alzheimers.
The findings from this study suggest that the diminished monocytic A clearance capacity is a consequence of the downregulation of key receptors involved in A phagocytosis within aging monocytes, the authors wrote. Collectively, these pieces of evidence indicate that the senescence of peripheral immune cells plays a critical role in the pathogenesis of AD, and rejuvenating peripheral immune cells in aging individuals may represent a promising intervention strategy.
As for the therapeutic value of young bone marrow transplants, the authors say there are many.
Not only did the young bone marrow improve the physical and behavioral symptoms of Alzheimers in older mice, but it decreased amyloid beta levels, lowered cerebral amyloid beta plaque and improved the mices overall cognition.
The findings also suggest that transplants can reverse one-third of Alzheimers-related gene expression, alleviate aged pathways, restore altered cell-to-cell communication in aging peripheral blood mononuclear cells, rescue dysfunctional monocytic functions and reduce levels of secreted triggers from aging cells called blood senescence-associated secretory phenotype or SASP factors.
The authors added that since young bone marrow transplants enhance the overall phagocytosis of monocytes, the same intervention is worth exploring for mice targeted by tau proteins, the other hallmark of Alzheimers. Future studies, they wrote, could focus on exploring other new strategies that can rejuvenate immune cells to advance the possibility of clinical translation.
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Stem cell transplants deliver promising treatments for mice with Alzheimer's disease - Courthouse News Service
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