In findings published in the journal Toxicology and Applied Pharmacology, US scientists explain how this naturally occurring compound, oleocanthal, beneficially alters the structure of highly toxic proteins known as ADDLs.
The researchers explain that ADDLs bind within the neural synapses of the brains of Alzheimer's patients and are believed to directly disrupt nerve cell function, eventually leading to memory loss, cell death and global disruption of brain function.
‘Binding of ADDLs to nerve cell synapses is thought to be a crucial first step in the initiation of Alzheimer's disease,’ said the lead research William L. Klein.
‘Oleocanthal alters ADDL structure in a way that deters the protein from binding to synapses.
Medical care costs
Currently, about 12 million people in the US plus the EU suffer from Alzheimer's, with some estimates predicting this figure will have tripled by 2050.
The direct and indirect cost of Alzheimer care is over $100 bn (€ 81 bn) in the US alone. The direct cost of Alzheimer care in the UK was estimated at £15 bn (€ 22 bn).
Reporting on a series of in vitro studies, the team of 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 said they next evaluated 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, the team said that they discovered that small amounts of oleocanthal effectively reduced short-term binding of ADDLs to hippocampal synapses, and additional studies revealed that oleocanthal can protect synapses from damage caused by ADDLs.
They reported that an unexpected finding of the research 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, they added.
‘In addition to aiding therapeutics, enhancing ADDL immunoreactivity also could increase the sensitivity of antibody-based Alzheimer's diagnostics,’ said the scientists.
The need for more research
According to the researchers, translational studies now are needed to link these laboratory findings to clinical interventions.
They said that future investigation of how exactly oleocanthal changes ADDL composition may increase the understanding of the structural component responsible for ADDL toxicity.
The scientists maintain that such insights could provide discovery pathways related to disease prevention and treatment.
‘Our findings may help identify effective preventative measures and lead to improved therapeutics in the fight against Alzheimer's disease,’ added the authors.
Source: Toxicology and Applied Pharmacology
Volume 240, Issue 2 October 2009
Title: Alzheimer's-associated Aβ Oligomers Show Altered Structure, Immunoreactivity and Synaptotoxicity with Low Doses of Oleocanthal.
Authors: J Pitt, W Roth, P Lacor, A B Smith III, M Blankenship, P Velasco, F De Felice, P Breslin, W. L. Klein