Department of Neurology, University of Rochester School of Medicine, Rochester, New York, USA.
1] Department of Oncology, Georgetown University Medical Center, Washington, DC, USA. [2] Department of Biochemistry, Georgetown University Medical Center, Washington, DC, USA.
Nat Med. 2014 Apr;20(4):415-8. doi: 10.1038/nm.3466. Epub 2014 Mar 9.
Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline. Biomarkers of preclinical disease will be critical to the development of disease-modifying or even preventative therapies. Unfortunately, current biomarkers for early disease, including cerebrospinal fluid tau and amyloid-β levels, structural and functional magnetic resonance imaging and the recent use of brain amyloid imaging or inflammaging, are limited because they are either invasive, time-consuming or expensive. Blood-based biomarkers may be a more attractive option, but none can currently detect preclinical Alzheimer's disease with the required sensitivity and specificity. Herein, we describe our lipidomic approach to detecting preclinical Alzheimer's disease in a group of cognitively normal older adults. We discovered and validated a set of ten lipids from peripheral blood that predicted phenoconversion to either amnestic mild cognitive impairment or Alzheimer's disease within a 2-3 year timeframe with over 90% accuracy. This biomarker panel, reflecting cell membrane integrity, may be sensitive to early neurodegeneration of preclinical Alzheimer's disease.
阿尔茨海默病导致进行性痴呆，目前全球有超过 3500 万人受其影响，预计到 2050 年将影响 1.15 亿人（参考文献 1）。目前尚无治愈方法或疾病修正疗法，这可能是由于我们无法在疾病进展导致明显记忆丧失和功能下降之前检测到它。临床前疾病的生物标志物对于开发疾病修正甚至预防性疗法至关重要。不幸的是，目前用于早期疾病的生物标志物，包括脑脊液 tau 和淀粉样蛋白-β 水平、结构和功能磁共振成像以及最近使用脑淀粉样蛋白成像或炎症老化，都受到限制，因为它们要么具有侵入性，要么耗时或昂贵。基于血液的生物标志物可能是一个更有吸引力的选择，但目前没有一种可以达到所需的敏感性和特异性来检测临床前阿尔茨海默病。在此，我们描述了我们的脂质组学方法，用于在一组认知正常的老年人中检测临床前阿尔茨海默病。我们发现并验证了一组来自外周血的十种脂质，它们可以在 2-3 年内以超过 90%的准确率预测表现出遗忘型轻度认知障碍或阿尔茨海默病的表型转化。该生物标志物面板反映了细胞膜的完整性，可能对临床前阿尔茨海默病的早期神经退行性变敏感。
