OBJECTIVE Type 2 diabetes and glucose metabolism have previously been linked to Alzheimer disease (AD). Yet, findings on the relation of glucose metabolism with amyloid-β and tau pathology later in life remain unclear. RESEARCH DESIGN AND METHODS We included 288 participants (mean age = 43.1 years, SD = 10.7, range 20–70 years) without dementia, from the Framingham Heart Study, who had available measures of glucose metabolism (i.e., one-time fasting plasma glucose and insulin) and positron emission tomography (PET) measures of amyloid-β and/or tau 14 years later. We performed linear regression analyses to test associations of plasma glucose (continuously and categorically; elevated defined as >100 mg/dL), plasma insulin, homeostatic model assessment for insulin resistance (HOMA-IR) with amyloid-β or tau load on PET. When significant, we explored whether age, sex, and APOE ε4 allele carriership (AD genetic risk) modified these associations. RESULTS Our findings indicated that elevated plasma glucose was associated with greater tau load 14 years later (B [95% CI] = 0.03 [0.01–0.05], P = 0.024 after false discovery rate [FDR] correction) but not amyloid-β. APOE ε4 carriership modified this association (B [95% CI] = −0.08 [−0.12 to −0.03], P = 0.001), indicating that the association was only present in APOE ε4 noncarriers (n = 225). Plasma insulin and HOMA-IR were not associated with amyloid-β or τ load 14 years later after FDR correction. CONCLUSIONS Our findings suggest that glucose metabolism is associated with increased future tau but not amyloid-β load. This provides relevant knowledge for prevention strategies and prognostics to improve health care.

中文翻译：

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14 年后，PET 上的葡萄糖代谢测量值与淀粉样蛋白-β 和 Tau 蛋白负荷之间的关联：弗雷明汉心脏研究的结果


目的 2 型糖尿病和葡萄糖代谢此前已被认为与阿尔茨海默病 (AD) 相关。然而，关于晚年葡萄糖代谢与淀粉样蛋白-β 和 tau 蛋白病理学关系的研究结果仍不清楚。研究设计和方法 我们纳入了弗雷明汉心脏研究中 288 名没有痴呆症的参与者（平均年龄 = 43.1 岁，SD = 10.7，范围 20-70 岁），他们有可用的葡萄糖代谢测量值（即一次性空腹血糖）和胰岛素）以及 14 年后淀粉样蛋白-β 和/或 tau 的正电子发射断层扫描 (PET) 测量。我们进行了线性回归分析，以测试血浆葡萄糖（连续且分类；升高定义为 >100 mg/dL）、血浆胰岛素、胰岛素抵抗稳态模型评估 (HOMA-IR) 与 PET 上淀粉样蛋白-β 或 tau 负荷的关联。当显着时，我们探讨了年龄、性别和 APOE ε4 等位基因携带（AD 遗传风险）是否改变了这些关联。结果我们的研究结果表明，14 年后，血浆葡萄糖升高与 tau 负载增加相关（B [95% CI] = 0.03 [0.01–0.05]，错误发现率 [FDR] 校正后 P = 0.024），但与淀粉样蛋白-β 无关。 APOE ε4 携带者改变了这种关联（B [95% CI] = -0.08 [-0.12 至 -0.03]，P = 0.001），表明该关联仅存在于 APOE ε4 非携带者中（n = 225）。 FDR 校正后 14 年后，血浆胰岛素和 HOMA-IR 与淀粉样蛋白-β 或 τ 负荷无关。结论 我们的研究结果表明，葡萄糖代谢与未来 tau 蛋白负荷增加相关，但与 β 淀粉样蛋白负荷无关。这提供了预防策略和预后的相关知识，以改善医疗保健。