Harvard Medical School, Boston, MA 02115, USA.
Department of Neurology, Weill Cornell Medicine and NewYork-Presbyterian, New York, NY 10065, USA.
Nutrients. 2021 Apr 19;13(4):1362. doi: 10.3390/nu13041362.
The 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 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 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 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 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 to adopt a lifestyle and nutrition plan geared towards Alzheimer's risk reduction.
等位基因是阿尔茨海默病最受研究的遗传风险因素，这种疾病的患病率正在上升，而且仍然没有治愈方法。针对代谢途径的精准营养靶向治疗为疾病的潜在预防提供了一种工具。然而，目前尚未进行针对 携带者的预防阿尔茨海默病的长期人体研究，以确定有效的营养方案。这可能是因为相对而言，人们对该遗传变异如何增加痴呆风险的具体机制还知之甚少。幸运的是，最近的研究开始关注这些机制。这些新数据为携带者通过生活方式和营养来减轻风险提供了一些推测的机会。在此，我们回顾了最近关于 如何差异化地影响小胶质细胞和炎症途径、星形胶质细胞和脂质代谢、周细胞和血脑屏障完整性以及胰岛素抵抗和葡萄糖代谢的发现。我们将这些数据用作基础，推测针对 携带者的精准营养方法，包括低血糖指数饮食加生酮选择、特定的地中海式食物选择以及七种营养补充剂。在可能的情况下，我们将基础科学机制与人类观察性研究相结合，为这种精准营养方法提供更完整和令人信服的理由。在最近的研究发现能够转化为长期人体研究之前，一种基于机制的实用临床方法可能对携带 基因的临床医生和患者有用，他们可以采用针对降低阿尔茨海默病风险的生活方式和营养计划。
