美国国家公共电台 NPR--Alzheimer's researchers are looking beyond plaques and tangles for new treatments

Alzheimer's researchers are looking beyond plaques¹ and tangles² for new treatments

Transcript³

The field of Alzheimer's research is branching out.

After decades of focusing on the sticky amyloid plaques and tangled⁴ tau fibers⁵ associated with the disease, brain researchers are searching for other potential causes of impaired⁶ memory and thinking.

That search is on full display this week at the Alzheimer's Association International Conference in San Diego, where sessions are exploring factors including genes⁷, brain injury, clogged⁸ arteries⁹ and inflammation.

A group of researchers from Seattle even unveiled a highly detailed¹⁰ atlas¹¹ showing how different types of brain cells change in Alzheimer's. The goal is to help scientists identify new approaches to treatment.

"Certainly, plaques and tangles are a hallmark," says Maria Carrillo, chief science officer of the Alzheimer's Association. "It doesn't mean plaques are the cause of cell death."

Plaques are clumps¹² of a protein called beta-amyloid that appear in the spaces between neurons. Tangles are made up of a protein called tau that appears inside a neuron.

Both proteins tend to accumulate in the brains of people with Alzheimer's. But their role in killing¹³ brain cells is still unclear.

Carrillo says the Alzheimer's field needs to look to cancer research where a deeper understanding of the disease has led to better treatments.

The shift comes after a series of experimental drugs have succeeded in removing amyloid plaques and tau tangles from the brain, but failed to halt the disease.

The Food and Drug Administration has approved one amyloid drug, Aduhelm, but is still evaluating whether it actually helps patients.

An Alzheimer's Atlas

The study that produced the atlas is emblematic¹⁴ of how researchers are recalibrating.

"What we're trying to do with this study is to look at cell vulnerability early on in disease, before [people] have plaques and tangles, before they have cognitive¹⁵ impairment," says Dr. C. Dirk Keene, a neuropathologist at the University of Washington.

To create the atlas, Keene and a team of researches analyzed¹⁶ more than a million cells from 84 brains donated by people who'd signed up for Alzheimer's research projects run by the University of Washington and Kaiser Permanente Washington Research Institute.

The brains came from donors¹⁷ "at all different stages of disease" Keene says, "so we can pinpoint¹⁸ what's happening from the earliest levels all the way through to people with advanced disease."

The effort is funded by the National Institute on Aging and grew out of the federal BRAIN initiative launched by President Obama in 2013.

The atlas came from the realization¹⁹ that "If we want to treat diseases of an extremely complex cellular²⁰ organ, you need to understand that organ much better than we do," says Ed Lein, a senior investigator²¹ at the Allen Institute for Brain Science, which played a key role in analyzing²² the brain tissue.

So the team spent years studying cells in healthy brains before looking at brains affected²³ by Alzheimer's.

"We've defined what a normal adult brain looks like," Lein says, "and now we can use that knowledge and look for changes that are happening in specific kinds of cells."

Finding vulnerable brain cells

At the Alzheimer's meeting, the team described changes they saw in more than 100 types of cells taken from the cortex — an area of the brain which is important to memory and thinking.

One finding was that neurons that make connections within the cortex itself were much more likely to die than those that connect to distant areas of the brain.

"What we're seeing is a profound effect on cortical circuitry that very plausibly²⁴ is the reason we have cognitive decline," Lein says.

If so, a treatment designed to protect those vulnerable neurons might prevent declines in memory and thinking linked to Alzheimer's.

The team also found a proliferation of brain cells that contribute to inflammation. These included certain immune cells and a type of cell that responds to injury.

"So while the neurons are lost, the non-neuronal cells are actually increasing and changing" Lein says.

The finding supports the idea that inflammation plays an important role in Alzheimer's, and that anti-inflammatory drugs might help protect the brain.

The Seattle team hopes other scientists will use the brain cell atlas to come up with new treatments for Alzheimer's.

"We've created an open-access resource where the whole community can come and look at this data," Lein says. "They can mine it to speed up progress in the field as a whole."

Speeding up progress is one reason Kyle Travaglini, a researcher at the Allen Institute, jumped at the chance to work on the Alzheimer's project.

"My grandmother started developing Alzheimer's disease when I was just going off to college," says Travaglini, who received his PhD in 2021.

Travaglini says the atlas project is appealing because it isn't based on a preconceived idea about what causes Alzheimer's.

"It's like looking at the same disease that everyone has been looking at but in an entirely²⁵ different way," he says.

1 plaques   

（纪念性的）匾牌( plaque的名词复数 )； 纪念匾； 牙斑； 空斑

参考例句：

• Primary plaques were detectable in 16 to 20 hours. 在16到20小时内可查出原发溶斑。
• The gondoliers wore green and white livery and silver plaques on their chests. 船夫们穿着白绿两色的制服，胸前别着银质徽章。

2 tangles   

（使）缠结， （使）乱作一团( tangle的第三人称单数 )

参考例句：

• Long hair tangles easily. 长头发容易打结。
• Tangles like this still interrupted their intercourse. 像这类纠缠不清的误会仍然妨碍着他们的交情。

3 transcript   

n.抄本，誊本，副本，肄业证书

参考例句：

• A transcript of the tapes was presented as evidence in court.一份录音带的文字本作为证据被呈交法庭。
• They wouldn't let me have a transcript of the interview.他们拒绝给我一份采访的文字整理稿。

4 tangled   

adj. 纠缠的，紊乱的 动词tangle的过去式和过去分词

参考例句：

• Your hair's so tangled that I can't comb it. 你的头发太乱了，我梳不动。
• A movement caught his eye in the tangled undergrowth. 乱灌木丛里的晃动引起了他的注意。

5 fibers   

光纤( fiber的名词复数 )； （织物的）质地； 纤维，纤维物质

参考例句：

• Thesolution of collagen-PVA was wet spined with the sodium sulfate as coagulant and collagen-PVA composite fibers were prepared. 在此基础上，以硫酸钠为凝固剂，对胶原-PVA共混溶液进行湿法纺丝，制备了胶原-PVA复合纤维。
• Sympathetic fibers are distributed to all regions of the heart. 交感神经纤维分布于心脏的所有部分。

6 impaired   

adj.受损的；出毛病的；有（身体或智力）缺陷的v.损害，削弱( impair的过去式和过去分词 )

参考例句：

• Much reading has impaired his vision. 大量读书损害了他的视力。 来自《现代汉英综合大词典》
• His hearing is somewhat impaired. 他的听觉已受到一定程度的损害。 来自《现代汉英综合大词典》

7 genes   

n.基因( gene的名词复数 )

参考例句：

• You have good genes from your parents, so you should live a long time. 你从父母那儿获得优良的基因，所以能够活得很长。 来自《简明英汉词典》
• Differences will help to reveal the functions of the genes. 它们间的差异将会帮助我们揭开基因多种功能。 来自英汉非文学 - 生命科学 - 生物技术的世纪

8 clogged   

（使）阻碍( clog的过去式和过去分词 )； 淤滞

参考例句：

• The narrow streets were clogged with traffic. 狭窄的街道上交通堵塞。
• The intake of gasoline was stopped by a clogged fuel line. 汽油的注入由于管道阻塞而停止了。

9 arteries   

n.动脉( artery的名词复数 )；干线，要道

参考例句：

• Even grafting new blood vessels in place of the diseased coronary arteries has been tried. 甚至移植新血管代替不健康的冠状动脉的方法都已经试过。 来自《简明英汉词典》
• This is the place where the three main arteries of West London traffic met. 这就是伦敦西部三条主要交通干线的交汇处。 来自《简明英汉词典》

10 detailed   

adj.详细的，详尽的，极注意细节的，完全的

参考例句：

• He had made a detailed study of the terrain.他对地形作了缜密的研究。
• A detailed list of our publications is available on request.我们的出版物有一份详细的目录备索。

11 atlas   

n.地图册，图表集

参考例句：

• He reached down the atlas from the top shelf.他从书架顶层取下地图集。
• The atlas contains forty maps,including three of Great Britain.这本地图集有40幅地图，其中包括3幅英国地图。

12 clumps   

n.（树、灌木、植物等的）丛、簇( clump的名词复数 )；（土、泥等）团；块；笨重的脚步声v.（树、灌木、植物等的）丛、簇( clump的第三人称单数 )；（土、泥等）团；块；笨重的脚步声

参考例句：

• These plants quickly form dense clumps. 这些植物很快形成了浓密的树丛。 来自《简明英汉词典》
• The bulbs were over. All that remained of them were clumps of brown leaves. 这些鳞茎死了，剩下的只是一丛丛的黃叶子。 来自《简明英汉词典》

13 killing   

n.巨额利润；突然赚大钱，发大财

参考例句：

• Investors are set to make a killing from the sell-off.投资者准备清仓以便大赚一笔。
• Last week my brother made a killing on Wall Street.上个周我兄弟在华尔街赚了一大笔。

14 emblematic   

adj.象征的，可当标志的；象征性

参考例句：

• The violence is emblematic of what is happening in our inner cities. 这种暴力行为正标示了我们市中心贫民区的状况。
• Whiteness is emblematic of purity. 白色是纯洁的象征。 来自辞典例句

15 cognitive   

adj.认知的，认识的，有感知的

参考例句：

• As children grow older,their cognitive processes become sharper.孩子们越长越大，他们的认知过程变得更为敏锐。
• The cognitive psychologist is like the tinker who wants to know how a clock works.认知心理学者倒很像一个需要通晓钟表如何运转的钟表修理匠。

16 analyzed   

v.分析( analyze的过去式和过去分词 )；分解；解释；对…进行心理分析

参考例句：

• The doctors analyzed the blood sample for anemia. 医生们分析了贫血的血样。 来自《简明英汉词典》
• The young man did not analyze the process of his captivation and enrapturement, for love to him was a mystery and could not be analyzed. 这年轻人没有分析自己蛊惑著迷的过程，因为对他来说，爱是个不可分析的迷。 来自《简明英汉词典》

17 donors   

n.捐赠者( donor的名词复数 )；献血者；捐血者；器官捐献者

参考例句：

• Please email us to be removed from our active list of blood donors. 假如你想把自己的名字从献血联系人名单中删去，请给我们发电子邮件。
• About half this amount comes from individual donors and bequests. 这笔钱大约有一半来自个人捐赠及遗赠。 来自《简明英汉词典》

18 pinpoint   

vt.准确地确定；用针标出…的精确位置

参考例句：

• It is difficult to pinpoint when water problems of the modern age began.很难准确地指出，现代用水的问题是什么时候出现的。
• I could pinpoint his precise location on a map.我能在地图上指明他的准确位置。

19 realization   

n.实现；认识到，深刻了解

参考例句：

• We shall gladly lend every effort in our power toward its realization.我们将乐意为它的实现而竭尽全力。
• He came to the realization that he would never make a good teacher.他逐渐认识到自己永远不会成为好老师。

20 cellular   

adj.移动的；细胞的，由细胞组成的

参考例句：

• She has a cellular telephone in her car.她的汽车里有一部无线通讯电话机。
• Many people use cellular materials as sensitive elements in hygrometers.很多人用蜂窝状的材料作为测量温度的传感元件。

21 investigator   

n.研究者，调查者，审查者

参考例句：

• He was a special investigator for the FBI.他是联邦调查局的特别调查员。
• The investigator was able to deduce the crime and find the criminal.调查者能够推出犯罪过程并锁定罪犯。

22 analyzing   

v.分析；分析( analyze的现在分词 )；分解；解释；对…进行心理分析n.分析

参考例句：

• Analyzing the date of some socialist countries presents even greater problem s. 分析某些社会主义国家的统计数据，暴露出的问题甚至更大。 来自辞典例句
• He undoubtedly was not far off the mark in analyzing its predictions. 当然，他对其预测所作的分析倒也八九不离十。 来自辞典例句

23 affected   

adj.不自然的，假装的

参考例句：

• She showed an affected interest in our subject.她假装对我们的课题感到兴趣。
• His manners are affected.他的态度不自然。

24 plausibly   

似真地

参考例句：

• The case was presented very plausibly. 案情的申述似很可信。
• He argued very plausibly for its acceptance. 他为使之认可辩解得头头是道。

25 entirely   

ad.全部地，完整地；完全地，彻底地

参考例句：

• The fire was entirely caused by their neglect of duty. 那场火灾完全是由于他们失职而引起的。
• His life was entirely given up to the educational work. 他的一生统统献给了教育工作。