Researchers have called for people donating tissue, organs, stem cells and blood to undergo genomic sequencing, following preclinical studies showing that Alzheimer’s disease can be transferred in bone marrow.
The team discovered an unexpected, transferable form of the neurodegenerative disease, which mice undergoing bone marrow transplantation developed at an accelerated rate.
The investigation challenges the idea that damaging beta amyloid peptides originate primarily in the brain and that Alzheimer’s occurs solely in familial or sporadic forms.
“This supports the idea that Alzheimer’s is a systemic disease where amyloids that are expressed outside of the brain contribute to central nervous system pathology,” said senior researcher Wilfred Jefferies, an immunologist at the University of British Columbia.
“As we continue to explore this mechanism, Alzheimer’s disease may be the tip of the iceberg and we need to have far better controls and screening of the donors used in blood, organ and tissue transplants as well as in the transfers of human derived stem cells or blood products.”
The findings, in the journal Stem Cell Reports, could however also provide the opportunity to develop new biomarkers for the disease.
Jefferies and co-workers initially obtained bone marrow containing stem cells from mice carrying a mutant human amyloid precursor protein (APP) transgene, which contributes to the characteristic amyloid plaques in Alzheimer’s disease.
This was transplanted into mice that either lacked the APP gene entirely or those carrying a normal version.
They found that the animals showed behavioral changes and signs of cognitive decline, such as the absence of usual fear and lack of short- and long-term memory, which appeared to be accelerated through transplantation.
Signs were present at six months after transplantation in the knockout mice and nine months in the normal mice, versus the 11 to 12 months that would be expected in this animal model of the disease.
Both groups of animals also showed distinct molecular and cellular hallmarks of Alzheimer’s disease, including blood-brain barrier dysfunction and beta amyloid extracellular deposits.
“In this study, we examined bone marrow and stem cells transplantation,” said Jefferies.
“However, next it will be important to examine if inadvertent transmission of disease takes place during the application of other forms of cellular therapies, as well as to directly examine the transfer of disease from contaminated sources, independent from cellular mechanisms.”
