The association of circulating endocannabinoids with neuroimaging and blood biomarkers of neuro-injury.
The association of circulating endocannabinoids with neuroimaging and blood biomarkers of neuro-injury.
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DOI：
10.1186/s13195-023-01301-x
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发表时间：
2023-09-12
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--
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临床前研究强调了内源性大麻素(内源性大麻素；ECB)在神经变性中的重要性。然而，之前的观察性研究关注的是有限的结果指标，只评估了很少的欧洲央行化合物，而在很大程度上忽视了欧洲央行体系的复杂性。我们研究了多种循环ECB和ECB样分子与神经退行性变和神经损伤的早期标志之间的关系，并测试了性别对效果的影响。这项探索性横断面研究包括从弗雷明翰心脏研究后代队列中随机抽取237名无痴呆症的老年参与者，他们参加了第9周期的检查(2011-2014)，年龄在65岁或以上，认知健康。采用高效液相色谱-高分辨质谱法对血清中的44种ECB化合物进行了定量。用线性回归模型检验ECB水平与脑MRI指标(即脑总体积、灰质体积、海马体积和白质高信号体积)以及阿尔茨海默病和神经损伤的血液生物标志物(总tau、神经丝光、胶质纤维酸性蛋白和泛素C末端水解酶L1)之间的关系。所有模型都调整了潜在的混杂因素，并检查了性别的影响修正。参与者的平均年龄为73.3 ± 6.2岁，其中40%为男性。经过对潜在混杂因素的调整和多重比较的校正后，在欧洲央行水平和研究结果之间没有观察到统计学上显著的关联。然而，我们发现了欧洲央行水平和不同研究结果之间的多种性别相关性。例如，高水平的亚油酰乙醇胺(LEA)与男性和女性的海马体积减少和增加有关(β ± SE = − 0.12 ± 0.06，p = 0.034和β ± SE = 0.08 ± 0.04，p = 0.026)。循环中的ECB可能在神经损伤中发挥作用，并可能解释大脑加速老化易感性的性别差异。特别是，我们的结果强调了来自N-酰基氨基酸和脂肪酸乙醇酰胺类的ECB可能参与其中，并提出了可能与大脑衰老有关的特定的新型脂肪酸化合物。此外，有必要研究ECB在人类阿尔茨海默病等神经退行性疾病中的作用，特别是通过前瞻性研究设计，并在包括绝经前妇女在内的不同人群中进行。网上版载有补充材料，可在10.1186/s13195-023-01301-x查阅。
Preclinical studies highlight the importance of endogenous cannabinoids (endocannabinoids; eCBs) in neurodegeneration. Yet, prior observational studies focused on limited outcome measures and assessed only few eCB compounds while largely ignoring the complexity of the eCB system. We examined the associations of multiple circulating eCBs and eCB-like molecules with early markers of neurodegeneration and neuro-injury and tested for effect modification by sex. This exploratory cross-sectional study included a random sample of 237 dementia-free older participants from the Framingham Heart Study Offspring cohort who attended examination cycle 9 (2011–2014), were 65 years or older, and cognitively healthy. Forty-four eCB compounds were quantified in serum, via liquid chromatography high-resolution mass spectrometry. Linear regression models were used to examine the associations of eCB levels with brain MRI measures (i.e., total cerebral brain volume, gray matter volume, hippocampal volume, and white matter hyperintensities volume) and blood biomarkers of Alzheimer’s disease and neuro-injury (i.e., total tau, neurofilament light, glial fibrillary acidic protein and Ubiquitin C-terminal hydrolase L1). All models were adjusted for potential confounders and effect modification by sex was examined. Participants mean age was 73.3 ± 6.2 years, and 40% were men. After adjustment for potential confounders and correction for multiple comparisons, no statistically significant associations were observed between eCB levels and the study outcomes. However, we identified multiple sex-specific associations between eCB levels and the various study outcomes. For example, high linoleoyl ethanolamide (LEA) levels were related to decreased hippocampal volume among men and to increased hippocampal volume among women (β ± SE = − 0.12 ± 0.06, p = 0.034 and β ± SE = 0.08 ± 0.04, p = 0.026, respectively). Circulating eCBs may play a role in neuro-injury and may explain sex differences in susceptibility to accelerated brain aging. Particularly, our results highlight the possible involvement of eCBs from the N-acyl amino acids and fatty acid ethanolamide classes and suggest specific novel fatty acid compounds that may be implicated in brain aging. Furthermore, investigation of the eCBs contribution to neurodegenerative disease such as Alzheimer’s disease in humans is warranted, especially with prospective study designs and among diverse populations, including premenopausal women. The online version contains supplementary material available at 10.1186/s13195-023-01301-x.
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DOI：
10.1016/j.jalz.2018.04.010
发表时间：
2018-09
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Buckley RF;Mormino EC;Amariglio RE;Properzi MJ;Rabin JS;Lim YY;Papp KV;Jacobs HIL;Burnham S;Hanseeuw BJ;Doré V;Dobson A;Masters CL;Waller M;Rowe CC;Maruff P;Donohue MC;Rentz DM;Kirn D;Hedden T;Chhatwal J;Schultz AP;Johnson KA;Villemagne VL;Sperling RA;Alzheimer's Disease Neuroimaging Initiative;Australian Imaging, Biomarker and Lifestyle study of ageing;Harvard Aging Brain Study
通讯作者：
Harvard Aging Brain Study
DOI：
10.1109/embc.2012.6345882
发表时间：
2012
期刊：
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
影响因子：
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作者：
Fletcher E;Carmichael O;Decarli C
通讯作者：
Decarli C
DOI：
10.1093/gerona/glac029
发表时间：
2022-02-03
影响因子：
5.1
作者：
Eastman, Jennifer;Bahorik, Amber;Yaffe, Kristine
通讯作者：
Yaffe, Kristine
影响因子：
18.2
作者：
Heifets BD;Castillo PE
通讯作者：
Castillo PE
DOI：
10.1002/alz.12154
发表时间：
2020-12
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Gustafson DR;Bäckman K;Scarmeas N;Stern Y;Manly JJ;Mayeux R;Gu Y
通讯作者：
Gu Y