Scientists at Stanford Medicine have tested a new potential treatment for Alzheimer’s disease in mice. The therapy involves transplanting blood stem cells from healthy mice into those with the disease, which helps replace defective neural cells.
Some forms of Alzheimer’s have been linked to certain gene variants in a type of brain cell called microglia. These are the resident immune cells of the brain, which keep watch over this vital organ for signs of pathogens, damage or metabolic waste build-up and get to work fixing it. The Stanford team focused on one particular gene called TREM2.
“Certain genetic variants of TREM2 are among the strongest genetic risk factors for Alzheimer’s disease,” said Marius Wernig, lead author of the study. “The data are convincing that microglial dysfunction can cause neurodegeneration in the brain, so it makes sense that restoring defective microglial function might be a way to fight neurodegeneration in Alzheimer’s disease.”
To investigate, the researchers experimented with mice that had defective TREM2 genes, giving them transplants of blood stem and progenitor cells from healthy mice. These transplanted cells were found to reconstitute the recipient’s blood system, and even formed new cells in the brain that looked and functioned like microglia.
Importantly, these new microglia-like cells replaced many of the recipient’s original microglia, and appeared to restore their function. It also reduced other markers of Alzheimer’s disease, including the build-up of amyloid plaques.
“We showed that most of the brain’s original microglia were replaced by healthy cells, which led to a restoration of normal TREM2 activity,” said Wernig. “Indeed, in the transplanted mice we saw a clear reduction in the deposits of amyloid plaques normally seen [in] TREM2-deficient mice.”
The researchers also say that the effects could be boosted by first engineering the transplant cells to have increased TREM2 activity. However, as promising as this proof-of-concept study might seem, there are still a few major caveats. Firstly, the replacement cells that grow are microglia-like, but aren’t exactly the same as natural microglia – a distinction that could potentially lead to other complications.
“These differences might in some way have their own detrimental effect,” said Wernig. “We have to look at that very carefully.”
The bigger issue is that the treatment would be invasive and risky for human use. Before new blood stem cells can be transplanted, a patient’s own native blood stem cells would need to be destroyed first, using radiation or chemotherapy. These are sometimes offered to leukemia patients, but are dangerous and unpleasant procedures. Less toxic methods are currently being investigated, and if any of these come to fruition the team says they might eventually be applied to their Alzheimer’s therapy.
The research was published in the journal Cell Stem Cell.
Source: Stanford Medicine