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.
This is a valuable piece of work. Perhaps immune system aging causes the innate immune system to fail to clear beta amyloid plaques. If so, restoring its proper function might turn out to be difficult because immune system rejuvenation might be necessary. Or perhaps a genetic difference causes the lower ability to remove the plaques. If so, perhaps a gene therapy could give the macrophages a capability that they lack.
Among the 7 Strategies for Engineered Negligible Senescence (SENS) to halting and rejuvenate bodies is the removal of accumulated extracellular junk. The amyloid plaque accumulations which likely cause Alzheimers are a form of extracellular junk and treatments to remove those plaques will likely be among the earliest rejuvenation treatments used in clinical practice. Because the amyloid plaques are associated with a major neurological disorder the development of means to remove them gets much more attention than some of the other SENS approaches. For example, little effort is going into the development of treatments to remove intracellular junk from lysosomes or to develop gene therapies to repair mitochondrial mutations.
|Share |||Randall Parker, 2005 June 13 02:22 PM Brain Alzheimers Disease|