10 June 2005
The human body has its own defense against brain aging: the innate immune system, which helps to clean the brain of amyloid-beta waste products. However, UCLA researchers discovered that some patients with Alzheimer's disease have an immune defect making it difficult to clean away these wastes. This may lead to over-saturation of the brain with amyloid beta, which form amyloid plaques, the definitive hallmark of Alzheimer's disease.
Published in the June 10 issue of the Journal of Alzheimer's Disease, the findings could lead to a new approach in diagnosing and treating Alzheimer's disease by helping to diagnose and correct this immune defect. This is the first time that researchers have discovered that the innate -- or more primitive -- part of the immune system may play a role in the development of Alzheimer's disease.
Using blood samples, investigators found that in healthy people, cells belonging to the innate immune system called macrophages, cleared amyloid-beta in a test tube test developed at UCLA. However, the macrophages of some Alzheimer's patients could not adequately perform this cleaning job.
"Macrophages are the janitors of the innate immune system, gobbling up waste products in the brain and throughout the body," said Dr. Milan Fiala, first author and UCLA researcher.
Fiala notes that there may be a problem either with the macrophages not effectively binding to amyloid beta or a problem in the absorption or uptake, which is called "phagocytosis." He adds that this immune defect may also be present in other diseases where a build-up of waste and plaques occur, such as in cardiovascular disease and Gaucher's disease.
"If further study shows that this defective macrophage function is present in most Alzheimer's disease patients, new hormonal or immune-boosting approaches may offer new approaches to treating the disease," adds Fiala.
Researchers add that this new approach differs from the amyloid-beta immunization method, which utilizes another part of the immune system called the adaptive immune system. According to Fiala, the immunization approach has resulted in amyloid-beta clearance in the lab in an animal model, but in a human clinical trial led to brain inflammation in a subset of patients.
In future studies, investigators plan to regulate the innate immune system by natural substances such as hormones, and natural products such as curcumin (from the curry powder). Currently in their lab, Fiala and Dr. George Bernard who is a professor in the UCLA Department of Oral Biology and Medicine,are testing the effectiveness of a naturally occurring hormone, called insulin-like growth factor I, in conjunction with a research team from the MP Biomedicals LLC Company.
The study was funded by the Alzheimer's Disease Association. The Sence Foundation and MP Biomedicals LLC Company are supporting current studies involved in testing the effectiveness of insulin-like growth factor I.
In addition, Fiala and MP Biomedicals LLC will also be exploring the development of an in-vitro diagnostic test for early detection of Alzheimer's disease.
Other investigators include: Dr. John Ringman, UCLA Department of Neurology, and Dr. Francesco Chiappelli in the UCLA Department of Oral Biology and Medicine.