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

譯者: Lilian Chiu 審譯者: Zoe Walmsley

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

全世界有數千萬人患有阿茲海默症，

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

一個讓腦部退化的大腦疾病，

逐漸摧毀患者的記憶力 和其他認知能力。

and other cognitive abilities.

It takes a heavy toll on both patients and families,

它對患者和家人造成沉重的負擔，

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

因為照顧患了阿茲海默症的家人，

在情緒上會很難承受， 在經濟上也會很辛苦。

and financially difficult.

While doctors have studied Alzheimer's for decades,

即使醫生已經研究 阿茲海默症數十年了，

conducting hundreds of clinical trials,

也進行過數百次臨床試驗，

there is still no effective preventive treatment or cure.

還是沒有找到有效的 預防性療法或解藥。

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

所以，阿茲海默症為何這麼難治療？

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

全世界的失智症患者中 有六成到八成患的是阿茲海默症。

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

失智症是個廣義詞，

指的是各種會影響到患者 記憶力、思維能力，

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

和日常起居能力的疾病。

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

大部分阿茲海默症患者會在 六十多歲時首次發現症狀，

experiencing mild memory problems,

覺察到輕微的記憶力問題，

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

比如搞不清日期還是 才剛聽到的東西立刻就忘了。

Some experience other changes, like frequent shifts in mood,

有些人會感覺到其他的轉變，

比如情緒多變、

increased anxiety and agitation,

焦慮和不安，

and problems with coping in new situations.

碰到狀況時不知所措等等。

Symptoms typically progress gradually over years

症狀通常會在數年間逐漸加重，

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

最終，阿茲海默症患者 可能會需要無時無刻的照護。

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

有幾種罕見的阿茲海默症 是由單一遺傳基因變異所引起。

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

但大多數情況下，

阿茲海默症的成因其實是 由多種基因與生活方式

of multiple genes in combination with lifestyle and environmental factors,

及環境因素產生的複雜交互作用，

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

因此無法預測出誰會得到這種疾病。

Alzheimer's involves a long, chronic process,

阿茲海默症涉及漫長的慢性病進程，

resulting in many changes to the brain,

過程中會給大腦造成許多改變，

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

可是改變可能會在出現症狀後的 十到二十年後才浮現。

So it's been difficult for scientists to pinpoint

因此，科學家很難精確地說

exactly what triggers this process

到底是什麼引發了這個病程，

and what causes the many symptoms of Alzheimer's.

以及阿茲海默症的症狀是甚麼造成的。

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

但多虧持續不斷的研究， 他們開始把線索拼湊起來。

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

科學家首先在阿茲海默症患者的大腦中

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

發現有乙型類澱粉蛋白 這種化合物的異常沉積。

Beta-amyloid is created when a large protein,

乙型類澱粉蛋白的形成 是由於另一個大型的蛋白──

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

簡稱 APP 的前類澱粉蛋白── 分解而產生的。

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

APP 在大腦中扮演重要的角色，

幫助腦神經的生長和修復。

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

然而，在阿茲海默症患者身上，

APP 沒有被妥當切割，

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

產生黏搭搭死纏在一起的 乙型澱粉樣蛋白的副產物。

These plaques can build up in the spaces between neurons,

這些斑塊就在 神經元之間的空間沉積，

and interfere with normal brain signaling.

干擾正常的大腦信號傳送。

But this likely isn't the full story.

但故事全貌可能不僅於此。

While all patients with Alzheimer's have plaques,

雖然所有阿茲海默症患者都有斑塊，

not all people with plaques have or will develop dementia.

但並非所有有斑塊的人都有、 或在未來會發展成失智症。

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

另外，阿茲海默症的症狀 也不見得會隨著腦中

as plaques accumulate in the brain.

斑塊的累積而變得更嚴重。

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

在 1980 年代，

也有研究發現另一種蛋白── 淘蛋白──也是可能的病灶。

Tau's normal role is as a scaffolding protein,

正常的情況下，淘蛋白 的角色是支架蛋白，

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

協助強化神經元的內部結構 並決定它們的形狀。

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

但阿茲海默症病患的淘蛋白 已經被修改過且有錯誤摺疊，

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

導致它變成乙型類澱粉蛋白那樣 黏呼呼並結成一團。

These tau tangles accumulate within neurons and are toxic,

這些纏在一起的淘蛋白 會在神經元內累積，

而且是有毒的，

causing the cells to eventually die.

最終導致細胞死亡。

In patients, plaques normally appear before tangles,

在患者身上，斑塊出現在糾結之前，

yet questions still remain.

但問題仍然沒得到解答。

Do amyloid plaques trigger tau dysfunction?

是類澱粉蛋白斑塊引發 淘蛋白功能失常嗎？

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

為什麼這些異常蛋白

導致這些特定的疾病症狀？

To make matters more complex,

更複雜的是，

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

近期的研究發現阿茲海默症

與一個名為微膠細胞的免疫細胞

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

改變其在大腦中的運作方式有關。

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

也有人發現阿茲海默症 還有另一個可能成因是

神經元之間的連結點── 突觸，出了問題。

in the junctions between neurons, called synapses.

And alterations in the way the brain produces and burns energy

大腦產生和燃燒能量的方式發生改變

may also be an underlying factor.

也可能是另一個潛在的成因。

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

把上述這些綜合起來， 意味著阿茲海默症

很可能是由一連串複雜的事件所引起。

by a complex cascade of events.

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

若要梳理出所有事件的發生順序，

及一旦開始後該如何阻止，

will take more research.

都還需要投入更多研究。

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

但患者還是有些方法去控制症狀。

Staying active, learning new skills,

保持活躍、學習新技能，

and even participating in daily activities,

即使只是參與日常活動，如做家務，

like household chores,

seems to slow disease progression.

都可能減緩疾病的惡化。

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

也有針對神經傳遞質（大腦中 發送訊號的分子）的藥物

can slow memory loss and help with learning and reasoning.

可以減緩記憶力喪失

並協助學習和推理。

And scientists continue to develop new therapies.

科學家也持續開發新的療法。

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

例如，有些很有潛力的 針對乙型類澱粉蛋白的藥物，

除了減緩疾病惡化，

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

還能減少斑塊在大腦中的累積。

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

短期內阿茲海默症應該不會消失不見。

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

失智症患者的人數 預計會在二十年內加倍。

But continued research holds the promise of better treatment

但持續的研究有望 開發出更好的治療方式，

and perhaps one day, prevention,

也許有一天，能做到預防，

as scientists piece the Alzheimer's puzzle together.

等科學家們成功拼齊 阿茲海默症的拼圖。