A naturally occurring compound found in extra-virgin olive oil has been found to alter the structure of neurotoxic proteins believed to contribute to the debilitating effects of Alzheimer’s disease. This structural change impedes the proteins’ ability to damage brain nerve cells.
Newly pressed extra-virgin olive oil contains oleocanthal, a compound whose pungency induces a strong stinging sensation in the throat, not unlike that caused by solutions of the non-steroidal anti-inflammatory drug ibuprofen. Oleocanthal and ibuprofen also have similar anti-inflammatory properties, and ibuprofen is associated with a decreased risk of Alzheimer’s disease when used regularly. However, the long-term side-effects of ibuprofen include damage to the kidneys and digestive system
“The findings may help identify effective preventative measures and lead to improved therapeutics in the fight against Alzheimer’s disease,” said study co-leader Paul A.S. Breslin,.
Known as ADDLs, these highly toxic proteins bind within the neural synapses of the brains of Alzheimer’s disease patients and are believed to directly disrupt nerve cell function, eventually leading to memory loss, cell death, and global disruption of brain function. Synapses are specialized junctions that allow one nerve cell to send information another.
“Binding of ADDLs to nerve cell synapses is thought to be a crucial first step in the initiation of Alzheimer’s disease. Oleocanthal alters ADDL structure in a way that deters their binding to synapses,” said William L. Klein, who co-led the research with Breslin. “Translational studies are needed to link these laboratory findings to clinical interventions.”
Klein and his colleagues identified ADDLs in 1998, leading to a major shift in thinking about the causes, progression and treatment of Alzheimer’s disease. Also known as beta-amyloid oligomers, ADDLs are structurally different from the amyloid plaques that accumulate in brains of Alzheimer’s disease patients.
Reporting on a series of in vitro studies, the researchers found that incubation with oleocanthal changed the structure of ADDLs by increasing the protein’s size.
Knowing that oleocanthal changed ADDL size, the researchers next examined whether oleocanthal affected the ability of ADDLs to bind to synapses of cultured hippocampal neurons. The hippocampus, a part of the brain intimately involved in learning and memory, is one of the first areas affected by Alzheimer’s disease.
Measuring ADDL binding with and without oleocanthal, they discovered that small amounts of oleocanthal effectively reduced binding of ADDLs to hippocampal synapses. Additional studies revealed that oleocanthal can protect synapses from structural damage caused by ADDLs.
An unexpected finding was that oleocanthal makes ADDLs into stronger targets for antibodies. This action establishes an opportunity for creating more effective immunotherapy treatments, which use antibodies to bind to and attack ADDLs.
Breslin commented on the implications of the findings. “If antibody treatment of Alzheimer’s is enhanced by oleocanthal, the collective anti-toxic and immunological effects of this compound may lead to a successful treatment for an incurable disease. Only clinical trials will tell for sure.”
References:
1. Paul A.S. Breslin, et al. Alzheimer’s-associated A? oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal. Toxicology and Applied Pharmacology, Volume 240, Issue 2, 15 October 2009, Pages 189-197.
