A new study from Massachusetts General Hospital (MGH) investigators provides additional evidence that amyloid-beta protein - which is deposited in the form of beta-amyloid plaques in the brains of patients with Alzheimer's disease - is a normal part of the innate immune system, the body's first-line defense against infection. Their study published in Science Translational Medicine finds that expression of human amyloid-beta (A-beta) was protective against potentially lethal infections in mice, in roundworms and in cultured human brain cells. The findings may lead to potential new therapeutic strategies and suggest limitations to therapies designed to eliminate amyloid plaques from patient's brains.It was to be expected that the A-beta had a function. The body rarely makes proteins without one, and it would not be widely found in nature if it wasn't needed. Still, this seems like a pretty important function, and it make the likelihood that just turning off or strongly suppressing the synthesis of A-beta will be a viable treatment for Alzheimers. It would be weird, indeed, if the problem with Alzheimer's ultimately trace back to infections or other immune responses that triggered the production of A-beta.
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A 2010 study co-led by Moir and Rudolph Tanzi, PhD, director of the MGH-MIND Genetics and Aging unit and co-corresponding author of the current study, grew out of Moir's observation that A-beta had many of the qualities of an antimicrobial peptide (AMP), a small innate immune system protein that defends against a wide range of pathogens. That study compared synthetic forms of A-beta with a known AMP called LL-37 and found that A-beta inhibited the growth of several important pathogens, sometimes as well or better than LL-37. A-beta from the brains of Alzheimer's patients also suppressed the growth of cultured Candida yeast in that study, and subsequently other groups have documented synthetic A-beta's action against influenza and herpes viruses.
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That superiority appears to relate to properties of A-beta that have been considered part of Alzheimer's disease pathology - the propensity of small molecules to combine into what are called oligomers and then aggregate into beta-amyloid plaques. While AMPs fight infection through several mechanisms, a fundamental process involves forming oligomers that bind to microbial surfaces and then clump together into aggregates that both prevent the pathogens from attaching to host cells and allow the AMPs to kill microbes by disrupting their cellular membranes. The synthetic A-beta preparations used in earlier studies did not include oligomers; but in the current study, oligomeric human A-beta not only showed an even stronger antimicrobial activity, its aggregation into the sorts of fibrils that form beta-amyloid plaques was seen to entrap microbes in both mouse and roundworm models.
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Says Tanzi, "While our data all involve experimental models, the important next step is to search for microbes in the brains of Alzheimer's patients that may have triggered amyloid deposition as a protective response, later leading to nerve cell death and dementia. If we can identify the culprits - be they bacteria, viruses, or yeast - we may be able to therapeutically target them for primary prevention of the disease."
Friday, May 27, 2016
Purpose of Alzheimer's Protein Found
Human amyloid-beta acts as natural antibiotic in the brains of animal models