Precision Nutrition for Preventing Alzheimer's Disease in ApoE4 Carriers

The ApoE4 allele is the most studied genetic risk factor for Alzheimer's disease, and the incidence of Alzheimer's disease is rising with no effective therapies currently available. Precision nutrition interventions targeting ApoE4-altered metabolic pathways provide a potential means of preventing this disease. However, there are currently no long-term human studies in ApoE4 carriers to determine effective nutritional protocols for preventing Alzheimer's disease. This may be because little is known about the specific mechanisms by which this genetic variant increases dementia risk.

A research review examines recent findings on how ApoE4 differentially affects microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood-brain barrier integrity, and insulin resistance and glucose metabolism; based on these data, a precision nutrition protocol for ApoE4 carriers is proposed, including a low glycemic index diet (optionally ketogenic diet), a specific Mediterranean diet, and seven nutritional supplements. We combine basic science mechanisms with human observational studies where possible to provide a more complete and compelling theoretical basis for this precision nutrition protocol.