Intranasal insulin modulates cerebrospinal fluid markers of neuroinflammation in mild cognitive impairment and Alzheimer's disease: a randomized trial.
Intranasal insulin modulates cerebrospinal fluid markers of neuroinflammation in mild cognitive impairment and Alzheimer's disease: a randomized trial.
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DOI：
10.1038/s41598-022-05165-3
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发表时间：
2022-01-25
影响因子：
4.6
通讯作者：
Craft S
中科院分区：
文献类型：
--
作者：
Kellar D;Register T;Lockhart SN;Aisen P;Raman R;Rissman RA;Brewer J;Craft S
鼻内胰岛素（INI）已在试点临床试验中显示出作为阿尔茨海默病（AD）治疗的前景。在最近的一项2期试验中，与安慰剂相比，使用两种输送装置之一接受INI治疗的轻度认知障碍（MCI）或AD参与者显示出改善的脑脊液（CSF）生物标志物特征和较慢的症状进展。在显示获益的队列中，我们测量了炎症、免疫功能和血管完整性的CSF标志物的变化，并评估了它们与认知、脑容量和CSF淀粉样蛋白和tau蛋白浓度变化的关系。在12个月的试验中，与安慰剂组相比，胰岛素治疗组的CSF干扰素-γ（p = 0.032）和嗜酸性粒细胞趋化因子（p = 0.049）增加，白细胞介素-6（p = 0.048）减少。在安慰剂组中观察到CSF巨噬细胞源性趋化因子增加的趋势（p = 0.083），在胰岛素治疗组中观察到白细胞介素-2增加的趋势（p = 0.093）。胰岛素治疗组和安慰剂组在CSF免疫/炎症/血管标志物的变化与认知、脑容量、淀粉样蛋白和tau蛋白浓度的变化之间显示出显著不同的关联模式。总之，INI治疗改变了AD中观察到的炎症和免疫功能标志物的典型进展，表明INI可能促进与治疗益处相关的代偿性免疫应答。
Intranasal insulin (INI) has shown promise as a treatment for Alzheimer’s disease (AD) in pilot clinical trials. In a recent phase 2 trial, participants with mild cognitive impairment (MCI) or AD who were treated with INI with one of two delivery devices showed improved cerebral spinal fluid (CSF) biomarker profiles and slower symptom progression compared with placebo. In the cohort which showed benefit, we measured changes in CSF markers of inflammation, immune function and vascular integrity and assessed their relationship with changes in cognition, brain volume, and CSF amyloid and tau concentrations. The insulin-treated group had increased CSF interferon-γ (p = 0.032) and eotaxin (p = 0.049), and reduced interleukin-6 (p = 0.048) over the 12 month trial compared to placebo. Trends were observed for increased CSF macrophage-derived chemokine for the placebo group (p = 0.083), and increased interleukin-2 in the insulin-treated group (p = 0.093). Insulin-treated and placebo groups showed strikingly different patterns of associations between changes in CSF immune/inflammatory/vascular markers and changes in cognition, brain volume, and amyloid and tau concentrations. In summary, INI treatment altered the typical progression of markers of inflammation and immune function seen in AD, suggesting that INI may promote a compensatory immune response associated with therapeutic benefit.
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DOI：
10.1038/nrneurol.2017.185
发表时间：
2018-03
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Arnold SE;Arvanitakis Z;Macauley-Rambach SL;Koenig AM;Wang HY;Ahima RS;Craft S;Gandy S;Buettner C;Stoeckel LE;Holtzman DM;Nathan DM
通讯作者：
Nathan DM
影响因子：
7.3
作者：
Chang YW;Hung LC;Chen YC;Wang WH;Lin CY;Tzeng HH;Suen JL;Chen YH
通讯作者：
Chen YH
影响因子：
16.6
作者：
Iturria-Medina Y;Sotero RC;Toussaint PJ;Mateos-Pérez JM;Evans AC;Alzheimer’s Disease Neuroimaging Initiative
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
影响因子：
3.7
作者：
Adzemovic MZ;Öckinger J;Zeitelhofer M;Hochmeister S;Beyeen AD;Paulson A;Gillett A;Thessen Hedreul M;Covacu R;Lassmann H;Olsson T;Jagodic M
通讯作者：
Jagodic M
影响因子：
9.2
作者：
Erta M;Quintana A;Hidalgo J
通讯作者：
Hidalgo J