(Nature早期偵測阿茲海默症) (APP)669–711/amyloid-β (Aβ)1–42 and Aβ1–40/Aβ1–42 ratios

報告：驗血就可提早發現阿茲海默症 時間：2018-02-01 1路透社 撰稿編輯：黃啟霖 報告：驗血就可提早發現阿茲海默症 路透社今天(1日)報導，日本和澳洲的研究人員共同表示，他們在研發一種檢驗血液方面取得重要進展，未來可以幫助醫生提早偵測出，哪些人有可能演變為阿茲海默症(Alzheimer's disease)患者。根據今天刊在「自然(Nature)」雜誌上的研究報告，科學家們表示，這項驗血可以偵測出一種有毒蛋白質，名為「腦中積存的澱粉質beta蛋白質(amyloid beta protein)」。這種蛋白質和阿茲海默症有關，在對大約370名患者進行的研究中，準確率超過90%。根據非營利組織國際失智症協會(Alzheimer's Disease International)，阿茲海默症最常見的形式「癡呆症」，影響了全球將近5千萬人，而預料在2050年以前，受到影響的人數會擴大到超過1億3,100萬人。目前，醫生都利用掃描大腦，或侵入性的腦脊髓液測試，也叫脊椎穿刺，試圖發現病人的大腦中是否堆積了澱粉質beta。但這些測試不但是侵入性，又很昂貴，而且也許只會顯示出這種疾病已經開始在發展。儘管經過數十年的科學研究，仍然沒有一種治療方法可以減緩阿茲海默症的發展。目前的藥物只能緩和某些症狀而已。根據這份報告的撰寫人、日本國家老年病學和老年醫學中心(NCGG)研究員柳澤勝彥(Katsuhiko Yanagisawa)指出，有簡單、低成本的驗血方法，可以讓醫藥公司找到夠多有發展成阿茲海默症風險的患者，以試驗他們研發的新藥，好對抗這種疾病。目前這種經由驗血找到可能發展成阿茲海默症的方式，有效性還有待評估。

High performance plasma amyloid-β biomarkers for Alzheimer's disease / Nature Published online: 31 January 2018 To facilitate clinical trials of disease-modifying therapies for Alzheimer's disease, which are expected to be most efficacious at the earliest and mildest stages of the disease1,2, supportive biomarker information is necessary. The only validated methods for identifying amyloid-β deposition in the brain—the earliest pathological signature of Alzheimer's disease—are amyloid-β positron-emission tomography (PET) imaging or measurement of amyloid-β in cerebrospinal fluid. Therefore, a minimally invasive, cost-effective blood-based biomarker is desirable3,4. Despite much effort3,4,5,6,7, to our knowledge, no study has validated the clinical utility of blood-based amyloid-β markers. Here we demonstrate the measurement of high-performance plasma amyloid-β biomarkers by immunoprecipitation coupled with mass spectrometry. The ability of amyloid-β precursor protein (APP)669–711/amyloid-β (Aβ)1–42 and Aβ1–40/Aβ1–42 ratios, and their composites, to predict individual brain amyloid-β-positive or -negative status was determined by amyloid-β-PET imaging and tested using two independent data sets: a discovery data set (Japan, n = 121) and a validation data set (Australia, n = 252 including 111 individuals diagnosed using 11C-labelled Pittsburgh compound-B (PIB)-PET and 141 using other ligands). Both data sets included cognitively normal individuals, individuals with mild cognitive impairment and individuals with Alzheimer's disease. All test biomarkers showed high performance when predicting brain amyloid-β burden. In particular, the composite biomarker showed very high areas under the receiver operating characteristic curves (AUCs) in both data sets (discovery, 96.7%, n = 121 and validation, 94.1%, n = 111) with an accuracy approximately equal to 90% when using PIB-PET as a standard of truth. Furthermore, test biomarkers were correlated with amyloid-β-PET burden and levels of Aβ1–42 in cerebrospinal fluid. These results demonstrate the potential clinical utility of plasma biomarkers in predicting brain amyloid-β burden at an individual level. These plasma biomarkers also have cost–benefit and scalability advantages over current techniques, potentially enabling broader clinical access and efficient population screening.   

 

Minimally invasive blood test for Alzheimer's disease February 1, 2018, Florey Institute of Neuroscience & Mental Health Scientists from Japan and Australia have teamed up to develop and validate a blood test for Alzheimer's disease, with the potential to massively ramp up the pace of Alzheimer's disease drug trials.   The blood test measures a specific peptide in the blood to inform scientists, with 90 percent accuracy, if a patient has the very earliest stages of Alzheimer's disease.  Blood samples from patients in a large study from the Japanese National Center for Geriatrics and Gerontology (NCGG) were initially analysed to identify the relevant peptides. Those indicating brain beta-amyloid burden were then tested against patient samples from the Australian Imaging, Biomarker and Lifestyle Study of Aging (AIBL), to validate the results. Professor Katsuhiko Yanagisawa, Director-general of Research Institute at NCGG, says: "Our study demonstrates the high accuracy, reliability and reproducibility of this blood test, as it was successfully validated in two independent large datasets from Japan and Australia." Dr. Koichi Tanaka at Shimadzu Corporation was instrumental in developing the initial blood testing procedure. Professor Tanaka won the Nobel prize in Chemistry in 2002 for the technique. "From a tiny blood sample, our method can measure several amyloid-related proteins, even though their concentration is extremely low. We found that the ratio of these proteins was an accurate surrogate for brain amyloid burden." One of the essential hallmarks of Alzheimer's disease is buildup of abnormal peptide in the brain, called beta-amyloid. The process starts silently about 30 years before outward signs of dementia, like memory loss or cognitive decline, have begun. Current tests for beta-amyloid include brain scans with costly radioactive tracers, or analysing spinal fluid taken via a lumbar puncture. These are expensive and invasive, and generally only available in a research setting. A diagnosis is usually made without these tools, by assessing a patient's range of symptoms. Laureate Professor Colin Masters of the Florey Institute of Neuroscience and Mental Health, and The University of Melbourne, has been at the forefront of Alzheimer's research since the 1980s. Professor Masters, who co-led the research published in the latest issue of Nature, says, "This new test has the potential to eventually disrupt the expensive and invasive scanning and spinal fluid technologies. In the first instance, however, it will be an invaluable tool in increasing the speed of screening potential patients for new drug trials." Progress in developing new therapeutic strategies for Alzheimer's disease has been disappointingly slow. None of the three drugs currently on the market treat the underlying disease. New drugs are urgently required, and the only way to do that is to speed up the whole process. That requires trials with rigorous and economical patient selection, to avoid recruiting patients who may not even have Alzheimer's disease. Due to the long timespans involved, pharmaceutical companies require accurate predictions of who is most at risk." 20-40 percent of the general elderly population over 70 years old have beta-amyloid buildup in their brain, and are considered to be "at risk" of developing Alzheimer's disease at some future point. Dementia is the second leading cause of death of Australians contributing to 5.4 percent of all deaths in males and 10.6 percent of all deaths in females each year In 2016 dementia became the leading cause of death among Australian females, surpassing heart disease which has been the leading cause of death for both males and females since the early 20th century. Females account for 64.4 percent of all dementia related deaths. Without a medical breakthrough, the number of people with dementia is expected to increase to 536,164 by 2025 and almost 1,100,890 by 2056 In 2018, dementia is estimated to cost Australia more than $15 billion. By 2025, the total cost of dementia is predicted to increase to more than $18.7 billion in today's dollars, and by 2056, to more than $36.8 billion The total estimated worldwide costs of dementia were US$818 billion in 2015