summary: Although Alzheimer’s disease has traditionally been considered a brain-centered condition, it may have a systemic origin and can be advanced by bone marrow transplantation from familial Alzheimer’s donors into healthy mice.
New research highlights the potential for disease transmission through cell therapy and suggests screening donors for Alzheimer’s disease markers to prevent inadvertent disease transmission.
By demonstrating that amyloid proteins of peripheral origin can induce Alzheimer’s disease in the central nervous system, this study shifts our understanding of Alzheimer’s disease to a more systemic perspective and calls for careful screening in transplants and blood transfusions. emphasizes the need for
Important facts:
- Systemic nature of Alzheimer’s disease: This study provides evidence that Alzheimer’s disease is thought to be systemic and that amyloid outside the brain contributes to its development.
- Effects of bone marrow transplant: Bone marrow stem cells from mice with inherited Alzheimer’s disease transferred Alzheimer’s disease to healthy mice, accelerating its onset.
- Implications for transplantation and transfusion: This finding advocates screening blood, organ, and stem cell donors for Alzheimer’s disease to avoid potential transmission of Alzheimer’s disease.
sauce: cell press
Familial Alzheimer’s disease can be transmitted through bone marrow transplants, researchers say in the journal March 28 stem cell report. When the research team transplanted bone marrow stem cells from mice with inherited Alzheimer’s disease into normal laboratory mice, the transplanted mice developed Alzheimer’s disease at an accelerated rate.
This study highlights the role of amyloid that originates outside the brain in the pathogenesis of Alzheimer’s disease, shifting the paradigm of Alzheimer’s disease from a disease produced exclusively in the brain to a more systemic disease. do.
Based on their findings, researchers say blood, tissue, organ, and stem cell donors should be screened for Alzheimer’s disease to prevent inadvertent transmission of Alzheimer’s disease during blood product transfusions and cell therapy. It states that there is.
“This supports the idea that Alzheimer’s disease is a systemic disease in which amyloid expressed outside the brain contributes to central nervous system pathology,” said senior author and immunologist at the University of British Columbia. Wilfred Jeffreys says:
“As we continue to study this mechanism, Alzheimer’s disease may be the tip of the iceberg, and we will be able to better manage and screen donors used for blood, organ and tissue transplants and human-derived stem cell transplants.” or blood products. ”
To test whether peripheral sources of amyloid may contribute to the development of Alzheimer’s disease in the brain, researchers investigated a familial version of the disease, a variant of the human amyloid precursor protein (APP) gene. ) were transplanted with bone marrow containing stem cells from mice carrying the disease. When this is cut, misfolded, and aggregates, it forms amyloid plaques, a hallmark of Alzheimer’s disease.
They carried out the transplants into two different strains of recipient mice: APP knockout mice that completely lacked the APP gene, and mice that carried a normal APP gene.
In this inherited Alzheimer’s disease model, mice typically begin developing plaques at 9 to 10 months of age and begin to show behavioral signs of cognitive decline at 11 to 12 months of age. Surprisingly, transplant recipients began to show symptoms of cognitive decline quite early, as early as 6 months post-transplant in the APP knockout mice and 9 months in the “normal” mice.
“The fact that we found significant behavioral differences and cognitive decline in APP knockout patients at 6 months was surprising, but also interesting, because it was not simply accelerated after transplantation. It’s just a symptom of the disease,” said Chaahat Singh, lead author of the paper. University of British Columbia.
In mice, signs of cognitive decline manifest as a lack of normal fear and loss of short- and long-term memory. Both groups of recipient mice also showed distinct molecular and cellular features of Alzheimer’s disease, including a leaky blood-brain barrier and amyloid accumulation in the brain.
After observing disease metastasis in APP knockout mice, which completely lack the APP gene, the research team concluded that the mutated gene in the donor cells could cause the disease, and that recipient animals carrying a normal APP gene The disease is suggested by observations of increased susceptibility to the disease. This disease can be transmitted even to healthy people.
The researchers demonstrated amyloid in the brains of APP knockout mice because the transplanted stem cells are hematopoietic cells, meaning they can grow into blood cells and immune cells, but not into neurons. , conclusively showing that Alzheimer’s disease may be caused by amyloid produced extracellularly. central nervous system.
Finally, the human APP gene is responsible for the disease in mice, indicating that mutated human genes can transmit disease to other species.
In future studies, the researchers will test whether transplanting tissue from normal mice into mice with familial Alzheimer’s disease can reduce the disease, and show that the disease is also transmitted through other types of transplants and blood transfusions. The plan is to test whether or not to expand research into disease transmission. Between the species.
“In this study, we investigated bone marrow and stem cell transplantation. But it is next important to examine whether inadvertent disease transmission is occurring during the application of other forms of cell therapy, and “It’s a direct look at the transmission of the disease from the source, independent of the mechanism,” Jeffries said.
Funding:
This research was supported by the Canadian Institutes of Health Research, the W. Garfield Weston Foundation/Weston Brain Institute, the Center for Blood Research, the University of British Columbia, the Austrian Academy of Sciences, and the Sullivan Urology Foundation at Vancouver General Hospital. .
About this genetics, Alzheimer’s disease, and transplant research news
author: Christopher Behnke
sauce: cell report
contact: Christopher Behnke – Cell Reports
image: Image credited to Neuroscience News
Original research: The findings appear below stem cell report
