腦中的鐵質或許可以預測阿茲海默氏症的病程


  【24drs.com】一篇新研究認為,腦中的鐵質程度可能可以預測帶有APOE ε4風險等位基因之阿茲海默氏症(AD)患者的疾病病程。
  
  研究作者、澳洲墨爾本大學Florey神經科學暨心智健康研究院資深研究員Ashley I. Bush博士表示,腦中的鐵質是AD疾病病程的一個被低估的驅動因子。
  
  測量腦中鐵質可用來預測疾病病程,降低腦中鐵質可能可作為一種新的治療標靶,藉以減緩疾病病程。
  
  他們的研究結果發表於二月JAMA Neurology期刊的來函中。
  
  研究者使用Alzheimer's Disease Neuroimaging Initiative (ADNI)資料庫的資料,該資料庫是始於2003年的公民合辦機構。
  
  ADNI的主要目標,是檢測serial MRI、正子放射斷層攝影、其他生物標記、以及臨床和神經心理學評估等是否可以合併使用於測量輕微認知缺損以及初期AD的病程。
  
  目前的研究探討了腦脊液(CSF)中的鐵蛋白程度-代表腦中的鐵質負擔,根據Bush博士指出,自1950年代就已知,鐵質升高是AD的病理特徵之一;鐵質上升可能會引起氧化壓力而損傷神經元。但是,我們以前沒有證據指出鐵質升高會實際地影響臨床表現。
  
  神經病學家最大的挑戰之一是,辨識最初期可能階段的AD患者,Bush博士表示,這些患者最可能對治療有反應。
  
  為了此篇研究,研究者分析了CSF的amyloid β 1-42 (Aβ 1-42)、tau、APOE、鐵蛋白、factor H (發炎標記)以及血紅素(血液滲漏標記)的含量。他們依據Rey氏聽覺-視覺學習任務(Rey Auditory-Visual Learning Task,RAVLT)以及阿茲海默氏症評估量表-認知分量表(ADAS-Cog13)(Alzheimer's Disease Assessment Scale-Cognitive subset[ADAS-Cog13])之檢測結果探討某段時間的認知。
  
  分析發現,對於認知正常的參與者,鐵蛋白值與認知惡化有關,以三種方式和時間與ε4等位基因相互影響(RAVLT: β = –1.58, P = .004; ADAS-Cog13: β = .11, P = .01)。
  
  根據ε4,認知正常個體的分類顯示,鐵蛋白值與ε4攜帶者的認知衰退強烈相關(RAVLT: β = –1.4, P < .001; ADAS-Cog13: β = .09, P = .02)。表現有APOE ε4等位基因者具有認知衰退的高風險,不過,並非所有人都會如此。
  
  Bush博士表示,研究發現,表現有APOE ε4風險等位基因的認知正常者中,高CSF鐵蛋白值幾乎可以完美地預言個人是否會在隨後的7年內經歷認知衰退。
  
  他表示,鐵蛋白的影響遠大於最廣為人知的生物標記— tau以及amyloid β。
  
  他們的結果也顯示,鐵質量低的APOE ε4攜帶者免於認知衰退。
  
  Bush博士表示,這是篇重要研究,因為它顯示,CSF的鐵蛋白值是預測帶有APOE ε4者在可預見的未來是否會惡化的一個極佳生物標記。
  
  Bush博士表示,CSF鐵蛋白或其他鐵質生物標記 — 例如,MRI技術如定量敏感性映射—可應用於診間以預測患者之認知能力下降的可能進展。
  
  他表示,這些生物標記也可用於臨床試驗招募。
  
  Bush博士等人即將啟動2b階段之臨床試驗,以確認deferiprone這項可通過腦部之螯合鐵質的藥物是否可以延緩阿茲海默氏症初期患者的疾病病程。
  
  資料來源:http://www.24drs.com/
  
  Native link:Brain Iron May Predict Progression in Alzheimer's
  
  

Brain Iron May Predict Progression in Alzheimer's

By Pauline Anderson
Medscape Medical News

A new study suggests brain iron levels may predict disease progression in patients with Alzheimer's disease (AD) who carry the APOE ε4 risk allele.

Iron in the brain is an "underappreciated driver of disease progression" in AD, study author Ashley I. Bush, MBBS, PhD, senior principal research fellow, Florey Institute of Neuroscience & Mental Health, University of Melbourne, Australia, told Medscape Medical News.

"Measuring brain iron could beused to predict disease progression, and lowering brain iron levels might present as a novel therapeutic target to slowthe disease process."

Their findings were described in a letter published in the January issue of JAMA Neurology.

The researchers used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, which was launched in 2003 as a public–private partnership.

The primary goal of ADNI is to test whether serial MRI, positron emission tomography, other biological markers, and clinical and neuropsychological assessments can be combined to measure the progression of mild cognitive impairment and early AD.

The current study looked at the level of ferritin in cerebrospinal fluid (CSF), which indicates the brain iron load. According to Dr Bush, it has been known since the 1950s that elevated iron is a pathologic feature of AD. Iron elevation, he said, may cause oxidative stress,which damages neurons.

"But wedidn't previously have evidence that iron elevation actually impacts on the clinical presentation,"he said.

Most Likely to Respond

One of the biggest challenges for neurologists is identifying patients with the earliest possible stages of AD. These patients, said Dr Bush, could be the most likely to respond to therapy.

For the study, researchers analysed CSF levels of amyloid β 1-42 (Aβ 1-42), tau, APOE, ferritin, factor H (an inflammatory marker), and hemoglobin (a blood leakage marker). They looked at cognitive performance over time on the Rey Auditory-Visual Learning Task (RAVLT) and the Alzheimer's Disease Assessment Scale-Cognitive subset (ADAS-Cog13).

The analysis found that for cognitively normal participants, the ferritin level was associated with cognitive deterioration in a three-way interaction with time and ε4 allele (RAVLT: β = –1.58, P = .004; ADAS-Cog13: β = .11, P = .01).

Categorization of cognitively normal individuals according to ε4 showed that ferritin level was strongly associated with cognitive decline in ε4 carriers (RAVLT: β = –1.4, P < .001; ADAS-Cog13: β = .09, P = .02).

People who express the APOE ε4 allele are at a high risk for cognitivedecline, although not all will do so.

"The study found that in cognitively normal people who express the APOE ε4 risk allele, high CSF ferritin almost perfectlypredicted whether the individual will experience cognitive decline in the subsequent 7 years," said Dr Bush.

The effect of ferritin "was far greater than the mostestablished biomarkers — tau and amyloid β," he said.

Their results also showed that APOE ε4 carriers who have low iron levels were protected from cognitive decline.

The study is important because it shows that the CSF ferritin level is "an excellent biomarker for predicting whether someone with APOE ε4 might progressin the foreseeable future," said Dr Bush.

CSF ferritin or other iron biomarkers — for example, MRI techniques, such as quantitative susceptibility mapping — could be used in the clinic to predict the likely progression of cognitive decline in patients, said Dr Bush.

These biomarkers could also be used forclinical trial recruitment, he said.

Dr Bush and colleagues will be launching a phase 2b clinical trial to determine whether deferiprone, a brain-permeable drug that chelates iron, can slow disease progression among patients in the early stagesof Alzheimer's disease.

Dr Bush is a shareholder in Prana Biotechnology Pty Ltd, Cogstate Pty Ltd, Eucalyptus Pty Ltd, Mesoblast Pty Ltd, Brighton Biotech LLC, Nextvet Ltd, Grunbiotics Pty Ltd, and Collaborative Medicinal Development LLC and a paid consultant for Collaborative Medicinal Development Pty Ltd. He and the other authors have filed a provisional patent encompassing findings from these data. Dr Bush has received funding relevant to this study from the Australian National Health and Medical Research Council, the Alzheimer's Association, Alzheimer's Research UK, the Michael J. Fox Foundation for Parkinson's Research, the Weston Brain Institute, and the Perpetual-Salteri Foundation.

JAMA Neurol. 2017;74):122-125.

    
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