The findings, presented in The Proceedings of the National Academy of Sciences (PNAS), suggest a link between a major genetic risk factor for Alzheimer's disease (AD) known as ApoE4 - which is present in about two-thirds of people who develop the disease - and the SirT1 protein that is targeted by resveratrol.
Led by Dr Rammohan Rao from the Buck Institute for Age Research, US, the research team found that ApoE4 causes a dramatic reduction in SirT1 in both cultured neural cells lines and in brain samples from patients with ApoE4 and AD.
In particular, the researchers discovered that the reduction in SirT1 was associated with a change in the way the amyloid precursor protein (APP) is processed. Rao said that ApoE4 favoured the formation of the amyloid-beta peptide that is associated with the sticky plaques that are one of the hallmarks of the Alzheimer's disease.
The group also found that the abnormalities associated with ApoE4 and Alzheimer's disease, such as the creation of phospho-tau and amyloid-beta plaques, could be prevented by increasing SirT1 - a shift that has already been suggested to be behind the suggested metabolic benefits of resveratrol.
"The biochemical mechanisms that link ApoE4 to Alzheimer's disease have been something of a black box. However, recent work from a number of labs, including our own, has begun to open the box," explained Dr Dale Bredesen, co-author of the study, and founder of the Buck Institute.
"This research offers a new type of screen for Alzheimer's prevention and treatment," added Rao. "One of our goals is to identify a safe, non-toxic treatment that could be given to anyone who carries the ApoE4 gene to prevent the development of AD."