Dietary lipids in the aetiology of Alzheimer's disease: implications for therapy.

Amyloid plaques and neurofibrillary tangles are the neuropathological hallmarks of Alzheimer's disease (AD), but no conclusive evidence has emerged showing that these hallmarks are the cause and not a product of the disease. Many studies have implicated oxidation and inflammation in the AD process, and there is growing evidence that abnormalities of lipid metabolism also play a role. Using epidemiology to elucidate risk factors and histological changes to suggest possible mechanisms, the hypothesis is advanced that dietary lipids are the principal risk factor for the development of late-onset sporadic AD. The degree of saturation of fatty acids and the position of the first double bond in essential fatty acids are the most critical factors determining the effect of dietary fats on the risk of AD, with unsaturated fats and n-3 double bonds conferring protection and an overabundance of saturated fats or n-6 double bonds increasing the risk. The interaction of dietary lipids and apolipoprotein E isoforms may determine the risk and rate of sustained autoperoxidation within cellular membranes and the efficacy of membrane repair. Interventions involving dietary lipids and lipid metabolism show great promise in slowing or possibly averting the development of AD, including dietary changes, cholesterol-modifying agents and antioxidants.