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

Translator: Hoi Ieng Chao Reviewer: Thomas Tam

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

全球有幾千萬人 患有阿茲海默病，

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

係種逐漸摧毀個人記憶 同其他認知能力嘅癱瘓性腦部疾病。

and other cognitive abilities.

It takes a heavy toll on both patients and families,

對患者同家庭都 都造成沉重負擔，

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

因為照顧患有阿茲海默症嘅摯愛 可能會令人感到情緒困擾，

and financially difficult.

同埋喺經濟上都好困難。

While doctors have studied Alzheimer's for decades,

雖然醫生已經研究咗 阿茲海默病數十年，

conducting hundreds of clinical trials,

並進行咗幾百項臨床試驗，

there is still no effective preventive treatment or cure.

但目前仍然冇有效嘅 預防或治癒方法。

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

點解阿茲海默症 咁難醫好呢？

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

阿茲海默病佔全球 所有癡呆症患者 60 到 80%。

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

癡呆症係一個更廣泛嘅術語， 用嚟描述多種不同病症。

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

呢啲病症會影響患者嘅記憶、 思維能力同日常功能。

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

大多數阿茲海默病患者 會喺 60 歲第一次注意到症狀，

experiencing mild memory problems,

經歷輕微嘅記憶問題，

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

例如唔記得日期 或者忘記剛學到嘅新嘢。

Some experience other changes, like frequent shifts in mood,

有啲人就會出現其他變化， 好似頻繁嘅情緒波動、

increased anxiety and agitation,

焦慮同容易激動，

and problems with coping in new situations.

喺應對新情況下出現問題。

Symptoms typically progress gradually over years

症狀通常會喺 幾年內逐漸惡化，

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

最終患有阿茲海默病嘅人 可能需要持續嘅照護。

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

一啲罕見嘅阿茲海默病 係由單一嘅遺傳基因變異引起。

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

但大多數情況下係由 多種基因嘅複雜相互作用，

of multiple genes in combination with lifestyle and environmental factors,

加上生活方式 同環境因素所造成嘅，

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

因此無辦法預測 邊個會發病。

Alzheimer's involves a long, chronic process,

阿茲海默病 係一個漫長嘅過程，

resulting in many changes to the brain,

導致大腦發生好多變化，

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

呢個過程可能喺症狀首次出現之前 10-20 年就已經開始。

So it's been difficult for scientists to pinpoint

科學家很難準確噉搵到

exactly what triggers this process

究竟係乜嘢觸發呢個過程，

and what causes the many symptoms of Alzheimer's.

以及造成阿茲海默症 多種症狀嘅原因。

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

但多得不斷嘅研究， 佢哋開始將呢個難題整理埋一齊。

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

最初，科學家注意到 阿茲海默病患者大腦

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

出現一種叫做 β-澱粉樣蛋白異常嘅積聚。

Beta-amyloid is created when a large protein,

β-澱粉樣蛋白係一種 大型蛋白質

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

澱粉樣 β 前體蛋白 或 APP 被分解時產生。

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

APP 係大腦扮演著重要角色， 有助於神經生長同修復。

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

然而係阿茲海默病患者， APP 嘅唔正確噉切割，

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

產生粘稠 β-澱粉樣蛋白副產品， 呢啲副產品容易聚集埋一齊。

These plaques can build up in the spaces between neurons,

呢啲斑塊可以喺 神經元之間嘅空隙積聚，

and interfere with normal brain signaling.

並干擾正常大腦信號嘅傳遞。

But this likely isn't the full story.

但呢啲並唔係整體嘅故事。

While all patients with Alzheimer's have plaques,

雖然所有阿茲海默病 患者都有斑塊，

not all people with plaques have or will develop dementia.

並唔係所有有斑塊嘅人 都會出現或將會發展成癡呆症。

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

即使隨著斑塊喺大腦累積， 症狀都未必變得更嚴重。

as plaques accumulate in the brain.

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

喺 1980 年代，另一種 蛋白 tau 被認為係可能嘅促成因素。

Tau's normal role is as a scaffolding protein,

Tau 嘅正常角色 係作為支架蛋白，

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

幫助加強神經元內部結構 並賦予佢哋嘅形狀。

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

但係阿茲海默病患者中， tau 蛋白會被修飾同錯誤摺疊，

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

令到佢好似 β-澱粉樣蛋白噉 一樣變得粘稠同埋結塊。

These tau tangles accumulate within neurons and are toxic,

tau 糾纏喺神經元內部積聚， 並具有毒性，

causing the cells to eventually die.

最終導致細胞死亡。

In patients, plaques normally appear before tangles,

患者嘅斑塊 通常喺糾結之前出現，

yet questions still remain.

但仍然存在一啲解唔開嘅問題。

Do amyloid plaques trigger tau dysfunction?

澱粉樣斑塊係咪會 引發 tau 蛋白功能障礙？

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

異常蛋白質點解 會導致呢啲症狀？

To make matters more complex,

更複雜嘅係，

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

最近研究發現，阿茲海默病

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

與大腦中叫做小膠質細胞嘅 免疫細胞功能變化密切相關。

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

其他研究就發現都可能係

in the junctions between neurons, called synapses.

由神經元之間嘅連接處， 即突觸，出現問題所引起。

And alterations in the way the brain produces and burns energy

而大腦產生同消耗能量嘅方式

may also be an underlying factor.

也可能係潛在因素。

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

所有呢啲因素都表明， 阿茲海默病可能係

by a complex cascade of events.

由一系列複雜嘅事件引起。

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

同埋引發事件嘅次序， 以及一旦開始要點樣阻止，

will take more research.

都需要更多研究。

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

然而患者可以採取一啲措施 更好噉管理症狀。

Staying active, learning new skills,

保持活躍、學習新技能，

and even participating in daily activities,

甚至參與日常活動，

like household chores,

如做家務，

seems to slow disease progression.

似乎都能減緩疾病嘅發展。

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

針對神經傳遞物質， 大腦信號分子嘅藥物

can slow memory loss and help with learning and reasoning.

可以減緩記憶嘅喪失， 並幫助學習和推理。

And scientists continue to develop new therapies.

科學家都不斷開發新療法。

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

例如，針對 β-澱粉樣蛋白嘅藥物

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

會減緩疾病進展 同減少大腦中斑塊積聚嘅希望。

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

阿茲海默病唔會 喺短期內消失。

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

預計係未來 20 年內， 癡呆症嘅病例將會增加一倍。

But continued research holds the promise of better treatment

但持續研究帶來 更好治療嘅希望，

and perhaps one day, prevention,

可能有一日可以實現預防。

as scientists piece the Alzheimer's puzzle together.

科學家們正喺度逐步解開 阿茲海默病嘅謎團。