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.
Highlights
Alzheimer’s disease (AD) is ascending the list of the top ten causes of death in the United States and remains the only one without a cure
Qi and colleagues [20] recently found that ApoE4 disrupts fatty acid metabolism coupling between neurons and astrocytes in an in vitro culture system, and this could contribute to an energy deficit and increase in AD risk
Mechanisms and emerging data suggest that adopting a lifestyle on the spectrum of low-glycemic index, low-carbohydrate, and ketogenic diets might help to protect against insulin resistance, inhibit pathological inflammatory processes (NLRP3 and CypA-NFκB-MMP9), and be an overall effective neuroprotective strategy in carriers of ApoE4
Summary
Alzheimer’s disease (AD) is ascending the list of the top ten causes of death in the United States and remains the only one without a cure. Southern Italians who carry ApoE4 but who live in the United States exhibit a highly reduced chance of living into late old age; odds ratio 0.29, p < 0.01 [9]. This is especially meaningful given that the median survival duration after AD diagnosis is 3.1–5.9 years [10]. (i) First, each of these studies employed a multidomain approach (recommendations for diet, exercise, cognitive engagement, etc.) While this is critical to maximally reduce AD risk in a clinical setting, it obscures the potential effects of nutrition . It is our hope that this manuscript is useful for clinicians and their patients, as well as an informative starting point for the development of future clinical trials
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