Boosting liver production of APOA1 reduced Alzheimer's-like signs in mouse brains
In mice, increasing APOA1 production in the liver raised its level in the brain, eased inflammation and improved spatial memory. The study appeared in Cell.
Proteins produced in the liver proved important for protecting the brain in mouse experiments on Alzheimer's disease, according to Наука.ua, which reports a study in the journal Cell. Impaired transport of these proteins across the blood-brain barrier was seen already in the early stages of the disease. Boosting liver production of one of them, APOA1, reduced signs of inflammation in brain cells and improved the spatial memory of the animals. nauka.ua
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Which proteins cross the blood-brain barrier
The blood-brain barrier is formed by the cells of the walls of brain blood vessels and associated structures, and it blocks most substances in the blood from reaching nervous tissue. Some molecules, insulin among them, can still cross it using dedicated receptors. Until now it remained unclear which blood proteins the barrier lets through and how they affect brain cells.
Of 861 proteins detected in blood plasma, only 92 entered the nervous tissue of the brain directly. A large share of them are involved in transport and in the regulation of metabolism and originate from the liver, adipose tissue and the intestine. Different protein types were distributed unevenly among brain cells. Apolipoprotein A1 (APOA1), which is synthesized in the liver and takes part in cholesterol transport, went mainly to astrocytes, the cells that support neurons. Through it, astrocytes could pass cholesterol on to neurons, maintaining the structure of synapses, the contacts through which nerve cells transmit signals.
What the mouse experiments showed
In mice with a genetically determined condition modeling Alzheimer's disease, the amount of APOA1 in astrocytes decreased while the blood-brain barrier was still intact. From this the authors concluded that in Alzheimer's disease the problem may lie not only in harmful substances crossing a damaged barrier, but also in an insufficient supply of useful proteins. nauka.ua
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When the researchers increased APOA1 production in the liver of these mice, its concentration also rose in brain tissue. After some time, lipid accumulation in astrocytes decreased, signs of inflammatory processes in the brain weakened, and the density of connections between neurons in the hippocampus and cortex increased. In behavioral tests, mice with raised APOA1 levels made fewer unnecessary movements and performed better in tests of spatial memory and novel object recognition.
The results were obtained in mice; the mechanism has not yet been confirmed in humans.
