A few studies provide evidence to suggest that the levels of amyloid-β in the brains of Alzheimer's patients are influenced by the levels of amyloid-β outside the brain. These are based on parabiosis, the process of joining the circulatory systems of two mice for an extended period of time, in this case one engineered to accumulate amyloid-β and exhibit the symptoms of Alzheimer's disease and the other normal. Given the additional capacity of the normal mouse to clear amyloid-β outside the brain, the engineered mouse improves, and researchers observed reduced levels of amyloid-β in the brain.
The research results noted here illustrate the opposite effect, that a mouse engineered to accumulate amyloid-β and exhibit the signs of Alzheimer's disease can export those symptoms to a normal mouse through their shared circulatory systems. Given everything else that is exchanged and mixed in the course of parabiosis, it is far from certain that an interpretation focused on transport of amyloid-β between mice is the correct one, however. Any number of other, intermediary proteins and mechanisms could be involved. Nonetheless, it is an interesting demonstration.
Alzheimer's disease, the leading cause of dementia, has long been assumed to originate in the brain. But new research indicates that it could be triggered by breakdowns elsewhere in the body. The findings offer hope that future drug therapies might be able to stop or slow the disease without acting directly on the brain, which is a complex, sensitive and often hard-to-reach target. Instead, such drugs could target the kidney or liver, ridding the blood of a toxic protein before it ever reaches the brain.
The scientists demonstrated this mobility through a technique called parabiosis: surgically attaching two specimens together so they share the same blood supply for several months. The team attached normal mice, which don't naturally develop Alzheimer's disease, to mice modified to carry a mutant human gene that produces high levels of a protein called amyloid-β. In people with Alzheimer's disease, that protein ultimately forms clumps, or "plaques," that smother brain cells. Normal mice that had been joined to genetically modified partners for a year "contracted" Alzheimer's disease. The amyloid-β traveled from the genetically-modified mice to the brains of their normal partners, where it accumulated and began to inflict damage.
Not only did the normal mice develop plaques, but also a pathology similar to "tangles" - twisted protein strands that form inside brain cells, disrupting their function and eventually killing them from the inside-out. Other signs of Alzheimer's-like damage included brain cell degeneration, inflammation, and microbleeds. In addition, the ability to transmit electrical signals involved in learning and memory - a sign of a healthy brain - was impaired, even in mice that had been joined for just four months. Besides the brain, amyloid-β is produced in blood platelets, blood vessels and muscles, and its precursor protein is found in several other organs. But until these experiments, it was unclear if amyloid-β from outside the brain could contribute to Alzheimer's disease. "The blood-brain barrier weakens as we age. That might allow more amyloid-β to infiltrate the brain, supplementing what is produced by the brain itself and accelerating the deterioration."