Some patients with Alzheimer’s disease have an immune system defect making it difficult to clean away amyloid-beta waste products in the brain.
This may lead to over-saturation of the brain with amyloid beta, which form amyloid plaques.

Published in the Journal of Alzheimer’s Disease, the findings of the researchers from University od California – Los Angeles ( UCLA ) 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 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.
Currently in their lab, Fiala and George Bernard at UCLA, are testing the effectiveness of a naturally occurring hormone, called insulin-like growth factor I ( IGF-I ).

Source: University of California – Los Angeles, 2005


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