Precision Nutrition for Alzheimer's Prevention in ApoE4 Carriers

Abstract

The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer's disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer's disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood-brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer's risk reduction.

Keywords: Alzheimer’s disease; ApoE4; astrocytes; blood–brain barrier; inflammation; insulin resistance; microglia; precision nutrition.

Figure 1

Precision nutrition for ApoE4 carriers. ApoE4 can contribute to NLRP3-mediated disease-associated microglia (DAM) formation, disease-associated astrocyte (DAA) formation, activation of the CypA-NFκB-MMP9 pathway in pericytes and loss of blood–brain barrier (BBB) integrity, and insulin resistance. The text described specific nutritional recommendations to target these pathways, including the following options: low-carbohydrate (LC) or ketogenic diets that generate βhB; extra virgin olive oil containing oleocanthal (OC) and hydroxytyrosol (HXT); cruciferous vegetables containing sulphoraphane (SFN); fatty fish containing DHA and DHA supplementation; Quercetin (Q) supplementation, also found in capers and red onions; resveratrol (R) supplementation; vitamins D₃ and K₂MK7 (DK) supplementation; vitamin B-complex (B); and low-dose lithium (Li) supplementation.