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Familial Alzheimer's Disease May Be Transmissible Through Stem Cell Transplantation in Preclinical Models


Core Concepts
Preclinical studies suggest that familial Alzheimer's disease may be transmissible through bone marrow stem cell transplantation, but the risk in human transplantation is considered low.
Abstract
The content discusses a study that found evidence of Alzheimer's disease (AD) pathology being transmissible through bone marrow stem cell transplantation in preclinical models. The key findings are: Transplantation of donor bone marrow stem cells carrying a mutant human amyloid precursor protein (APP) transgene into both APP-deficient and healthy wild-type mice resulted in the rapid development of AD pathological hallmarks. These included compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment. The symptoms of cognitive decline presented more rapidly in the transplanted mice compared to typical AD transgenic mice. The researchers suggest this reveals an "unexpected transmissible form of AD" and raises the possibility of "iatrogenic transmission in AD patients" through procedures involving stem cell transplantation. However, several experts caution that the relevance to human transplantation is limited. They note that the familial form of AD is extremely rare, and there are already safeguards in place for stem cell transplantation. The experts do not believe the risks extend to other procedures like organ transplantation or blood transfusion.
Stats
Symptoms of cognitive decline presented 6 months after transplant in APP-knockout mice and 9 months in wild-type mice, compared to 12 months in typical AD transgenic mice.
Quotes
"Contrary to prevailing beliefs regarding AD occurring solely in familial or sporadic forms, our study reveals an unexpected transplantable form of AD in a preclinical model, suggesting potential iatrogenic transmission in AD patients." "human donors of blood, tissue, organ, and stem cells should be screened to prevent its inadvertent transfer of disease during blood product transfusions and cellular therapies."

Deeper Inquiries

What are the potential mechanisms by which familial Alzheimer's pathology could be transmitted through stem cell transplantation?

The potential mechanisms by which familial Alzheimer's pathology could be transmitted through stem cell transplantation involve the transfer of mutant human amyloid precursor protein (APP) transgenes from donor bone marrow stem cells to the recipient. This transfer results in the rapid development of Alzheimer's disease (AD) pathologic hallmarks in preclinical models. These pathologic features include compromised blood-brain barrier integrity, heightened cerebral vascular neoangiogenesis, elevated brain-associated beta-amyloid levels, and cognitive impairment. The presence of these mutant genes in the transplanted stem cells can lead to the manifestation of AD pathology in the recipient.

How might these findings impact the screening and safety protocols for stem cell and other tissue/organ transplantation procedures?

These findings could impact the screening and safety protocols for stem cell and other tissue/organ transplantation procedures by highlighting the importance of screening human donors for potential genetic mutations associated with familial Alzheimer's disease. To prevent inadvertent transmission of the disease during blood product transfusions and cellular therapies, it may be necessary to implement screening measures to identify donors carrying the mutant genes linked to AD. This would help mitigate the risk of transmitting AD pathology through stem cell transplantation and other related procedures, ensuring the safety of recipients.

Could this discovery lead to new insights into the underlying causes and propagation of Alzheimer's disease, beyond just the familial form?

This discovery could indeed lead to new insights into the underlying causes and propagation of Alzheimer's disease beyond just the familial form. The study's demonstration that beta-amyloid accumulation originating outside of the central nervous system contributes to AD pathology opens up avenues for the development of new biomarkers for AD. By showing that bone marrow cells can transfer the gene and the disease in a specific experimental context, the research sheds light on potential mechanisms of AD propagation. While the relevance to human organ and cell transplant may be limited, the findings offer valuable insights into the broader understanding of AD pathogenesis and the role of genetic mutations in disease transmission.
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