Stanford Medicine researchers are hopeful that a proof-of-concept treatment in mice — blood stem cell transplants — may reduce signs of Alzheimer’s disease.

Despite extensive research on Alzheimer’s, what causes the neurodegenerative disorder and how it develops are not well understood. Most therapies focus on clearing the buildup of amyloid plaques found in the brains of people with Alzheimer’s disease, though it is not clear if these plaques are merely a sign of Alzheimer’s pathology or are directly causing dementia.

There is, however, a clear association between nonfamilial Alzheimer’s disease, which tends to strike later in life and does not stem from an inherited gene variant, and various mutations in microglia. Microglia cells protect other brain cells against invaders and function as a cleanup crew, taking out the metabolic trash that can accumulate in the brain.

TREM2 transplant
In the study, mice with a defective TREM2 gene received hematopoietic stem and progenitor cell transplants from mice with normal TREM2 function. The researchers found that the transplanted cells reconstituted the blood system and that some of them efficiently incorporated into the recipients’ brains and became cells that looked and behaved like microglia.

In addition, the current procedure would be highly risky if it were developed for human therapy because transplantation of blood stem cells requires the recipient to undergo a highly toxic chemotherapy or radiation treatment to kill off native blood stem cells. However, many researchers, including some at the Institute for Stem Cell Biology and Regenerative Medicine, are developing less toxic methods of preconditioning patients for stem cell transplants. A brain cell therapy could then piggyback on such improved and safer transplantation methods.

Source: https://med.stanford.edu/news/all-news/2023/09/stem-cell-alzheimers.html