Why is Alzheimer’s disease so difficult to treat? - Krishna Sudhir

翻译人员: Liwen Huang 校对人员: Gia Hwang

Around the world, tens of millions of people have Alzheimer's disease,

全球有数千万人患有阿尔茨海默病，

a debilitating brain disorder that gradually destroys a person's memory

一种脑功能紊乱疾病，

它会逐渐摧毁一个人的记忆力 和其他认知能力。

and other cognitive abilities.

It takes a heavy toll on both patients and families,

它给患者和家属都造成了重大的影响，

as caring for a loved one with Alzheimer's can be emotionally overwhelming

因为照顾患有阿尔茨海默病的亲人

可能会让人在情感上难以承受,

and financially difficult.

经济上也很困难。

While doctors have studied Alzheimer's for decades,

尽管医生研究阿尔茨海默病已数十年，

conducting hundreds of clinical trials,

进行了数百次临床试验，

there is still no effective preventive treatment or cure.

但仍无有效的预防治疗或治愈方法。

So, why is Alzheimer's disease so difficult to treat?

那为什么阿尔茨海默病这么难治呢？

Alzheimer's accounts for 60 to 80% of all dementia patients worldwide.

阿尔茨海默病患者

占全球所有痴呆患者的 60-80％。

Dementia is a broader term, used to describe a variety of conditions

痴呆是一个更广义的术语，

用于描述各种影响患者记忆力、

that affect a patient's memory, thinking skills, and everyday functions.

思维能力和日常功能的疾病。

Most Alzheimer's patients first notice symptoms in their 60s,

大多数阿尔茨海默病患者

在 60 多岁时初次察觉到症状，

experiencing mild memory problems,

有轻微的记忆问题，

like losing track of dates or forgetting what they just learned.

如忘记约会或忘记刚学的东西；

Some experience other changes, like frequent shifts in mood,

有些会经历其他变化，

如频繁的情绪变化、更加焦虑不安，

increased anxiety and agitation,

and problems with coping in new situations.

以及难以应对新情况的问题。

Symptoms typically progress gradually over years

症状通常会随着时间推移逐渐恶化，

and eventually a person with Alzheimer's may require constant care.

最终阿尔茨海默病患者 可能需要持续的护理。

Some rare forms of Alzheimer's are caused by a single inherited gene variant.

一些罕见的阿尔茨海默病类型

是由单一遗传基因变异引起的，

But most of the time Alzheimer's is due to the complex interaction

但大多数情况下，阿尔茨海默病

是由多个基因复杂的相互作用

of multiple genes in combination with lifestyle and environmental factors,

以及生活方式和环境因素导致的，

so it's impossible to predict who will develop the disease.

因此无法预测谁会患病。

Alzheimer's involves a long, chronic process,

阿尔茨海默病是长期而慢性的过程，

resulting in many changes to the brain,

会导致大脑的许多变化，

that likely starts to unfold at least 1 to 2 decades before symptoms first appear.

可能在症状初次出现前 至少十到二十年就开始了。

So it's been difficult for scientists to pinpoint

因此，科学家们很难确定

exactly what triggers this process

究竟是什么触发了这一过程，

and what causes the many symptoms of Alzheimer's.

什么导致了阿尔茨海默病的许多症状。

But thanks to continued research, they're beginning to put this puzzle together.

但得益于持续不断的研究，

他们开始将这一拼图拼凑起来。

Initially, scientists noticed that the brains of Alzheimer's patients

最初，科学家注意到，

阿尔茨海默病患者的大脑中

display an abnormal buildup of a compound called beta-amyloid.

出现一种化合物的异常积聚，

叫做 β 淀粉样蛋白。

Beta-amyloid is created when a large protein,

分解产生 β 淀粉样蛋白的大蛋白

amyloid-beta precursor protein, or APP, is broken down.

即淀粉样 β 前体蛋白（APP）。

APP plays an essential role in the brain, aiding in neural growth and repair.

APP 在大脑中起着至关重要的作用，

有助于神经生长和修复。

However, in Alzheimer's patients, it's thought that APP is improperly cleaved,

但是，在阿尔茨海默病患者中，

APP 被认为裂解异常，

creating sticky beta-amyloid byproducts, which easily clump together.

产生了粘稠、易聚集的 β 淀粉样蛋白副产物。

These plaques can build up in the spaces between neurons,

斑块堆积在神经元之间的空隙中，

and interfere with normal brain signaling.

干扰正常的大脑信号传递，

But this likely isn't the full story.

但这可能并非全部的原因。

While all patients with Alzheimer's have plaques,

虽然所有阿尔茨海默病患者都有斑块，

not all people with plaques have or will develop dementia.

但并非所有有斑块的人 都痴呆或会痴呆。

And Alzheimer's symptoms don't always become more severe

阿尔兹海默病的症状

as plaques accumulate in the brain.

亦并非随着脑中斑块的积聚而加重。

In the 1980s, another protein, tau, emerged as a possible contributor.

二十世纪八十年代，

另一种蛋白 TAU 蛋白 成为可能的致病因素。

Tau's normal role is as a scaffolding protein,

TAU 蛋白通常作为支架蛋白，

to help reinforce the internal structure of neurons and give them their shape.

帮助强化神经元的内部结构 并赋予其形状。

But in Alzheimer's patients, tau is modified and misfolded,

但在阿尔茨海默病患者中，

TAU 蛋白被改变和错误折叠，

causing it, like beta-amyloid, to become sticky and to clump.

导致其像 β 淀粉样蛋白一样 变得粘稠并聚集。

These tau tangles accumulate within neurons and are toxic,

这些 TAU 蛋白缠结积聚 在神经元内且具有毒性，

causing the cells to eventually die.

导致细胞最终死亡。

In patients, plaques normally appear before tangles,

在患者中，斑块通常出现在缠结之前，

yet questions still remain.

因而仍然存在疑问。

Do amyloid plaques trigger tau dysfunction?

淀粉样蛋白斑块

会引发 TAU 蛋白功能障碍吗？

And why exactly do these abnormal proteins lead to such specific disease symptoms?

究竟为什么这些异常蛋白

会导致这样特定的疾病症状？

To make matters more complex,

更复杂的是，

recent studies have found that Alzheimer's is closely linked to changes

最近的研究发现，阿尔茨海默病

与被称为小胶质细胞的免疫细胞

in the way immune cells, called microglia, function in the brain.

在大脑中的功能变化密切相关。

Others have found that Alzheimer's may also be caused by problems

其他研究发现，阿尔茨海默病

也可能是由被称为“突触”的

in the junctions between neurons, called synapses.

神经元之间连接部位的问题引起的。

And alterations in the way the brain produces and burns energy

大脑产生和消耗能量方式的改变

may also be an underlying factor.

也可能是一个潜在的因素。

Together, all this suggests that Alzheimer's is likely caused

所有这些共同表明，

阿尔茨海默病

by a complex cascade of events.

可能是由一连串复杂的事件引起的。

And teasing out the order of events, and how to stop it once it starts,

要弄清楚事件的顺序，

以及事件开始后如何让它停止，

will take more research.

还需要更多的研究。

But there are things patients can do to better manage symptoms.

但是患者可以做些事情

以更好地控制症状，

Staying active, learning new skills,

多活动、学习新技能，

and even participating in daily activities,

甚至参与日常活动

like household chores,

如做家务，

seems to slow disease progression.

似乎可以减缓疾病的进展。

Medications that target neurotransmitters, the brain's signaling molecules,

针对大脑信号分子即神经递质的药物

can slow memory loss and help with learning and reasoning.

可以减缓记忆丧失，

并有助于学习和推理。

And scientists continue to develop new therapies.

科学家们继续开发新的疗法，

For example, drugs that target beta-amyloid have shown promise

例如，β 淀粉样蛋白靶向药物

有望减缓疾病、减少脑中斑块积聚。

in slowing the disease and reducing plaque accumulation in the brain.

Alzheimer's disease won't go away anytime soon.

阿尔茨海默病不会很快消失，

Dementia cases are expected to double in the next 20 years.

预计未来 20 年痴呆患者将翻一番。

But continued research holds the promise of better treatment

但是，随着科学家们拼出 阿尔茨海默病的谜题拼图，

and perhaps one day, prevention,

持续的研究有望带来更好地治疗方法，

as scientists piece the Alzheimer's puzzle together.

也许有一天，能预防阿尔茨海默病。