Study finds familial Alzheimer’s disease is transmitted through bone marrow transplants

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. As we continue to study this mechanism, Alzheimer’s disease may be the tip of the iceberg, and we will better manage donors used for blood, organ, and tissue transplants, as well as human-derived stem cells and stem cell transplants. Must be screened. Blood products. ”

Wilfred Jeffreys, senior author and immunologist at the University of British Columbia

To test whether peripheral sources of amyloid contribute to the development of Alzheimer’s disease in the brain, researchers investigated familial versions of the disease, namely those carrying variants of the human amyloid precursor protein (APP) gene. transplanted bone marrow containing stem cells from mice. When this is cut, misfolded, and aggregates, it forms amyloid plaques, a hallmark of Alzheimer’s disease. They performed transplants into two different strains of recipient mice: her APP knockout mice, which 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 showing symptoms of cognitive decline much earlier. 6 months post-transplant for APP knockout mice and 9 months for “normal” mice.

“The fact that APP knockout patients showed significant behavioral differences and cognitive decline at six months was surprising but also interesting, as it suggests that the disease was accelerated after transplantation. We’re just showing you what’s going on,” 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, it was demonstrated that the human APP gene is responsible for the disease in mice, and that mutated human genes can transmit the 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 will be important next to find out whether inadvertent disease transmission occurs during the application of other forms of cell therapy, and “It’s a direct look at disease transmission, from the source of the contamination, and independent from the cellular machinery,” Jeffries said.

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. .