Insulin Resistance is Associated with Increased Levels of Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Reduced Memory Function in At-Risk Healthy Middle-Aged Adults.
Insulin Resistance is Associated with Increased Levels of Cerebrospinal Fluid Biomarkers of Alzheimer's Disease and Reduced Memory Function in At-Risk Healthy Middle-Aged Adults.
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DOI：
10.3233/jad-160110
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发表时间：
2016-04-12
期刊：
影响因子：
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通讯作者：
Bendlin BB
中科院分区：
文献类型：
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作者：
Hoscheidt SM;Starks EJ;Oh JM;Zetterberg H;Blennow K;Krause RA;Gleason CE;Puglielli L;Atwood CS;Carlsson CM;Asthana S;Johnson SC;Bendlin BB
2 型糖尿病与阿尔茨海默病 (AD) 的风险增加有关。调节正常的胰岛素功能对于降低 AD 所致痴呆的患病率可能很重要，特别是对于具有 AD 遗传风险或有 AD 父母家族史的个体。胰岛素抵抗 (IR) 和 AD 病理学之间的关系仍然知之甚少，特别是在临床代谢疾病或认知能力下降之前的中年。我们研究了以 HOMA-IR 为索引的 IR、AD 病理学的脑脊液 (CSF) 生物标志物和患有 AD 的中年人记忆之间的关联。我们假设较高的 HOMA-IR 和 APOE ε4 携带量与较大的 CSF AD 病理和较差的记忆性能相关。来自威斯康星州阿尔茨海默病研究中心的无认知症状中年人（N = 70，平均年龄 = 57.7 岁），其父母有 AD 痴呆家族史，接受了腰椎穿刺、抽血和神经心理学测试。针对 HOMA-IR 和 APOE ε4 状态检查了 CSF AD 生物标志物，包括可溶性淀粉样蛋白前体蛋白 β (sAPP-β)、β-淀粉样蛋白 42 (Aβ42) 和磷酸化 tau (P-tau181)。根据 HOMA-IR、CSF AD 生物标志物和 APOE ε4 状态检查延迟记忆性能。较高的 HOMA-IR 与较高的 sAPP-β 和 Aβ42 相关。与非携带者相比，APOE ε4 携带者的 sAPP-α、sAPP-β 和 P-tau181/Aβ42 水平显着较高。较高的 HOMA-IR 和 CSF AD 病理学同时存在预示着更差的延迟记忆性能。总体而言，研究结果表明 IR 和 APOE ε4 是中年 AD 病理学发展的促成因素，并为将胰岛素功能作为 AD 潜在可改变危险因素提供支持。
Type 2 diabetes is associated with an increased risk for Alzheimer disease (AD). Regulation of normal insulin function may be important in reducing the prevalence of dementia due to AD, particularly in individuals who harbor genetic risk for or have a parental family history of AD. The relationship between insulin resistance (IR) and AD pathology remains poorly understood, particularly in midlife prior to the onset of clinical metabolic disease or cognitive decline. We examined associations between IR as indexed by HOMA-IR, cerebral spinal fluid (CSF) biomarkers of AD pathology and memory in middle-aged adults enriched for AD. We postulated that higher HOMA-IR and APOE ε4 carriage would be associated with greater CSF AD pathology and poor memory performance. Cognitively asymptomatic middle-aged adults (N=70, mean age=57.7 years) from the Wisconsin Alzheimer’s Disease Research Center with a parental family history of dementia due to AD underwent lumbar puncture, blood draw and neuropsychological testing. CSF AD biomarkers including soluble amyloid precursor protein β (sAPP-β), β–amyloid42 (Aβ42) and phosphorylated tau (P-tau181) were examined with respect to HOMA-IR and APOE ε4 status. Delayed memory performance was examined with respect to HOMA-IR, CSF AD biomarkers and APOE ε4 status. Higher HOMA-IR was associated with higher sAPP-β and Aβ42. APOE ε4 carriers had significantly higher levels of sAPP-α, sAPP-β and P-tau181/Aβ42 compared to noncarriers. The concurrent presence of higher HOMA-IR and CSF AD pathology predicted worse delayed memory performance. Overall, the findings suggest that IR and APOE ε4 are contributing factors to the development of AD pathology in midlife, and provide support for targeting insulin function as a potentially modifiable risk factor for AD.