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Hereditary Alzheimer’s Transmitted Via Bone Marrow Transplants

Summary: Alzheimer’s disease, traditionally considered a brain-centered disease, may have systemic origins and can be accelerated by bone marrow transplants from donors with familial Alzheimer’s disease into healthy mice.

A new study highlights the potential transmission of the disease via cell therapies and suggests screening donors for Alzheimer’s disease markers to prevent accidental transfer of the disease.

By demonstrating that amyloid proteins from peripheral sources can induce Alzheimer’s disease in the central nervous system, this research shifts the understanding of Alzheimer’s disease to a more systemic perspective, highlighting the need for careful screening during transplants and blood transfusions.

Highlights:

  1. Systemic nature of Alzheimer’s disease: The study provides evidence that Alzheimer’s disease can be considered systemic, with amyloids located outside the brain contributing to its development.
  2. Impact of bone marrow transplants: Bone marrow stem cells from mice suffering from a hereditary form of Alzheimer’s transferred the disease to healthy mice, thus accelerating its onset.
  3. Implications for transplants and transfusions: The results argue in favor of screening blood, organ and stem cell donors for Alzheimer’s disease to avoid its potential transmission.

Source: Cell Press

Familial Alzheimer’s disease can be transferred via bone marrow transplant, researchers show March 28 in the journal Stem Cell Reports. When the team transplanted bone marrow stem cells from mice carrying an inherited version of Alzheimer’s disease into normal laboratory mice, the recipients developed Alzheimer’s disease at an accelerated rate. .

The study highlights the role of amyloid that originates outside the brain in the development of Alzheimer’s disease, changing the paradigm of Alzheimer’s disease from a disease exclusively produced in the brain to a more systemic disease.

Based on their findings, the researchers say that donors of blood, tissues, organs and stem cells should be screened for Alzheimer’s disease to avoid its inadvertent transfer during transfusions of blood products and cell therapies.

“This supports the idea that Alzheimer’s disease is a systemic disease in which amyloids expressed outside the brain contribute to central nervous system pathology,” says lead author and immunologist Wilfred Jefferies, of the University of British Columbia.

“As we continue to explore this mechanism, Alzheimer’s disease may be just the tip of the iceberg and we need to have much better controls and screening of donors used in blood transplants, of organs and tissues as well as in transfers of stem cells of human origin or blood products.

To test whether a peripheral source of amyloid might contribute to the development of Alzheimer’s disease in the brain, the researchers transplanted bone marrow containing stem cells from mice carrying a familial version of the disease, a variant of human amyloid precursor protein (APP) gene, which, when split, misfolded and aggregated, form the amyloid plaques characteristic of Alzheimer’s disease.

They performed transplants into two different strains of recipient mice: APP knockout mice lacking the APP gene and mice carrying a normal APP gene.

In this model of hereditary Alzheimer’s disease, mice typically begin to develop plaques between 9 and 10 months of age, and behavioral signs of cognitive decline begin to appear between 11 and 12 months of age. Surprisingly, transplant recipients started showing symptoms of cognitive decline much earlier: 6 months after transplantation for APP knockout mice and 9 months for “normal” mice.

“The fact that we could observe significant behavioral differences and cognitive decline in APP knockouts at 6 months was surprising but also intriguing because it simply showed disease onset accelerating after transfer.” , says first author Chaahat Singh of the University of British Columbia.

In mice, signs of cognitive decline include a lack of normal fear and loss of short- and long-term memory. Both groups of recipient mice also had clear molecular and cellular features of Alzheimer’s disease, including leaks in the blood-brain barrier and accumulation of amyloid in the brain.

By observing the transfer of disease in APP knockout mice lacking the APP gene, the team concluded that the mutated gene in the donor cells can cause the disease and by observing that recipient animals carrying an APP gene normal are susceptible to the disease, suggesting that the disease can be transmitted to healthy people.

Since the transplanted stem cells were hematopoietic cells, meaning they could develop into blood and immune cells but not neurons, the researchers’ demonstration of the presence of amyloid in the brains of knockout mice APP definitively shows that Alzheimer’s disease can result from amyloid produced outside the body. the central nervous system.

Finally, the source of the disease in mice is a human APP gene demonstrating that the mutated human gene can transfer the disease to a different species.

In future studies, the researchers plan to test whether transplanting tissue from normal mice into mice with familial Alzheimer’s disease could alleviate the disease and to check whether the disease is also transmissible via other types of transplants or of transfusions and to expand the investigation into the transfer of the disease. between species.

“In this study, we looked at bone marrow and stem cell transplantation. However, it will next be important to examine whether accidental disease transmission occurs when applying other forms of cell-based therapies, as well as to directly examine disease transfer from contaminated sources, independent of cellular mechanisms. “, explains Jefferies.

Funding:

This research was funded 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 news on research in genetics, Alzheimer’s disease and transplantation

Author: Kristopher Benke
Source: Cell Reports
Contact: Kristopher Benke – Cell Reports
Picture: Image is credited to Neuroscience News

Original research: The results will appear in Stem Cell Reports

News Source : neurosciencenews.com
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