The heart-brain adage comes from epidemiological studies that show that people with cardiovascular risk factors such as high-blood pressure and elevated cholesterol levels, may be more at risk for Alzheimer’s and other dementias.
This connection between heart and brain has also led to some disappointments: clinical trials of lipid-lowering statins have not helped patients diagnosed with Alzheimer’s, although epidemiological studies suggest that long-term use of the drugs may help prevent Alzheimer’s and other dementias.
The link between head and heart is still being pursued because new Alzheimer’s drugs have failed time and again. One approach that is now drawing some interest looks at the set of proteins that carry around fats in the brain. These lipoproteins could potentially act as molecular sponges that mop up the amyloid-beta peptide that clogs up connections among brain cells in Alzheimer’s.
One of these proteins—Apolipoprotein J, also known as clusterin—intrigues researchers because of the way it interacts with amyloid-beta and the status of its gene as a risk factor for Alzheimer’s.
A researcher from the University of Minnesota, Ling Li, recently presented preliminary work at the Alzheimer’s Drug Discovery Foundation annual meeting that showed that, at least in a lab dish, a molecule made up of a group of amino acids from APOJ is capable of protecting against the toxicity of the amyloid-beta peptide. It also quelled inflammation and promoted the health of synapses—the junctions where one brain cell encounters another. Earlier work by another group showed that the peptide prevented the development of lesions in the blood vessels of animals.
Li's research will still require crossing a number of conceptual barriers to prove that an APOJ-derived drug can actually work in humans. APOJ plays different roles in Alzheimer’s. In the healthy brain, it may help preserve the normal workings of brain cells, but it may also promote the Alzheimer's disease process under other conditions.
From the preliminary results, Li hopes that the APOJ-derived peptide will harness the beneficial effects of the protein. The work is still in early stages and Li and her team now plan to go on to test the peptide in mice. “The long term goal would be to find something that prevents or treats Alzheimer’s,” she says. An APOJ protein fragment—or a variety of other new ideas for drug candidates—are badly needed for a disease that affects tens of millions of people worldwide yet lacks any good treatment.
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